Chemical Composition of Achillea millefolium L. and Their Anti-Inflammatory Activity.

A new monoterpene, (-)-10-hydroxydihydroactinidiolide (1), along with two known monoterpenes, loliolide (2) and (+)-isololiolide (3), three known megastigmanes, 3a-hydroxy-5ß,6ß-epoxy-ß-ionone (4), 3a-hydroxy-5a,6a-epoxy-ß-ionone (5), and (+)-dehydrovomifoliol (6), an eudesmane-type sesquiterpene, 4a-hydroxy-4ß-methyldihydrocostol (7), a monoterpene, 8-hydroxycarvotanacetone (8), two flavonoids,  chrysoeriol (9) and apigenin (10), and a phenylpropanoid, 3-(4-hydroxyphenyl)-1-propanol (11), were isolated from the whole plant of Achillea millefolium. The structure of compound 1 was identified according to spectroscopic data of HRMS and NMR, and its absolute configuration was assigned by 13C NMR calculations with DP4+ probability analyses and ECD calculations. The absolute configuration of compound 6 was determined by ECD calculations. Compounds 3, 6, 9 and 10 could dose-dependently inhibited the NO release in LPS-induced RAW267.4 cells.

seco-iridoid glycosides and flavonoid glycosides from the Gentiana olivieri Griseb and their anti-inflammatory activities.

Three undescribed seco-iridoid glycosides, one undescribed flavonoid glycoside, and three known glycosides were isolated and identified from Gentiana olivieri Griseb. The structures of these compounds were determined through spectroscopic analysis and ECD calculations. Olivierisecosides NP (1-3) were identified as aromatic conjugated seco-iridoid glucosides, among them olivierisecoside N was representing a particularly rare subtype known as the morroniside seco-iridoids. The compounds 2, 3, 5, and 6 exhibited significant inhibition of COX-2 expression, particularly compound 5 which demonstrated the most pronounced inhibitory activity with IC50 value of 23.33 ± 0.51 µM. This study provides evidence for the potential development and utilization of G. olivieri as a source of anti-inflammatory components.

Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. METHODS: We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. RESULTS: Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported. CONCLUSIONS: Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed. TRAIL REGISTRATION: ChiCTR2200063759, September 16, 2022.

Comparison of metagenomic next-generation sequencing and conventional culture for the diagnostic performance in febrile patients with suspected infections.

BACKGROUND: Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration. METHODS: This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared. RESULTS: Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p < 0.001) and negative predictive value (54.67% vs. 42.9%) of mNGS were superior to those of culture. In contrast, the culture exhibited higher specificity (99.27% vs. 85.40%, p < 0.001) and positive predictive value (98.84% vs. 87.01%) than mNGS. Among infected patients with positive mNGS results, 64 received adjusted antibiotic therapy including treatment transitions, antibiotic downgrading, and combination therapy. Among them, 9 had additional antifungal drugs and 21 patients had a treatment turning point based on the mNGS results and these patients recovered and discharged due to timely antibiotic adjustment. Both positive rates of puncture fluid mNGS and tissue mNGS were higher than those of culture in the patients who had prior antibiotic use, and this difference was statistically significant (p = 0.000). CONCLUSION: mNGS is more sensitive and accurate than traditional culture, making it ideal for identifying pathogens and screening infectious diseases, especially for those with uncultivated or difficult-to-cultivate species. Early diagnosis allows for prompt treatment with targeted antibiotics, and mNGS is recommended when samples are limited.

Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis, and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function and provides a novel therapeutic strategy for MAFLD prevention and treatment.

Light-Mediated Multilevel Flexible High-Efficiency Perovskite Resistive Switching Memory Based on Mn:CsPbCl3 Nanocrystals.

Herein, the electrical characteristics, photoelectric properties, resistive switching (RS) mechanism, and flexible storage application of Ag/PMMA&Mn:CsPbCl3/ITO (PMMA = poly(methyl methacrylate)) devices are studied by using the photoelectric material Mn:CsPbCl3 nanocrystals (NCs) embedded in PMMA as the RS layer. The devices exhibit bipolar RS behavior with low operating voltage, excellent cycling endurance (>1000 times), long retention time (≥104 s), high ON/OFF ratio (≈104), and good environmental stability. The flexible memory devices have demonstrated reliable mechanical stability of consecutive 1000 bending cycles. In addition, multilevel data storage is realized by introducing the UV light, and the adjustive resistive switching characteristics is achieved through photoelectric synergistic work. The resistive switching mechanism under the excitation of light has been studied comprehensively. This work may pave a new way for developing the next generation of high-density data storage and photoelectric memristor.

Disseminated Talaromyces marneffei infection associated with haemophagocytic syndrome in an HIV-negative patient in northern China: a case report.

BACKGROUND: Talaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients. CASE PRESENTATION: A 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient's infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure. CONCLUSION: Although rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about "new" infections in nonendemic areas.

Optimization of the cavity length and pulse characterization based on germanene as a saturable absorber in an Er-doped fiber laser.

In this study, germanene-nanosheets (NSs) were synthesized by liquid-phase exfoliation, followed by an experimental investigation into the nonlinear saturable absorption characteristics and morphological structure of germanene. The germanene-NSs were employed as saturable absorbers, exhibiting saturation intensity and modulation depth values of 22.64M W/c m 2 and 4.48%, respectively. This demonstrated the feasibility of utilizing germanene-NSs passively mode-locked in an erbium-doped fiber laser (EDFL). By optimizing the cavity length, improvements in the output of EDFL characteristics were achieved, resulting in 883 fs pulses with a maximum average output power of 19.74 mW. The aforementioned experimental outcomes underscore the significant potential of germanene in the realms of ultrafast photonics and nonlinear optics.

Guaianolide-type sesquiterpene lactones from Achillea millefolium L. and their anti-inflammatory activity.

Seventeen undescribed guaianolide sesquiterpene lactones, millefoliumines A-Q, and seven known analogues were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated based on the HRESIMS and NMR data analyses. The absolute configurations of millefoliumines A-Q were determined by single-crystal X-ray crystallography, ECD data analysis along with quantum-chemical ECD calculations. The anti-inflammatory effects of these compounds on the LPS-induced RAW264.7 cell model were evaluated. As a result, millefoliumine G exhibited potential inhibitory effects on the release of NO, the level of pro-inflammatory cytokines including TNF-α and IL-6. Above results indicated a potential of the guaianolides from A. millefolium in the anti-inflammatory drug development.

Multi-material electrospinning: from methods to biomedical applications.

Electrospinning as a versatile, simple, and cost-effective method to engineer a variety of micro or nanofibrous materials, has contributed to significant developments in the biomedical field. However, the traditional electrospinning of single material only can produce homogeneous fibrous assemblies with limited functional properties, which oftentimes fails to meet the ever-increasing requirements of biomedical applications. Thus, multi-material electrospinning referring to engineering two or more kinds of materials, has been recently developed to enable the fabrication of diversified complex fibrous structures with advanced performance for greatly promoting biomedical development. This review firstly gives an overview of multi-material electrospinning modalities, with a highlight on their features and accessibility for constructing different complex fibrous structures. A perspective of how multi-material electrospinning opens up new opportunities for specific biomedical applications, i.e., tissue engineering and drug delivery, is also offered.

Neural substrate underlying the learning of a passage with unfamiliar vocabulary and syntax.

Speech comprehension is a complex process involving multiple stages, such as decoding of phonetic units, recognizing words, and understanding sentences and passages. In this study, we identify cortical networks beyond basic phonetic processing using a novel passage learning paradigm. Participants learn to comprehend a story composed of syllables of their native language, but containing unfamiliar vocabulary and syntax. Three learning methods are employed, each resulting in some degree of learning within a 12-min learning session. Functional magnetic resonance imaging results reveal that, when listening to the same story, the classic temporal-frontal language network is significantly enhanced by learning. Critically, activation of the left anterior and posterior temporal lobe correlates with the learning outcome that is assessed behaviorally through, e.g. word recognition and passage comprehension tests. This study demonstrates that a brief learning session is sufficient to induce neural plasticity in the left temporal lobe, which underlies the transformation from phonetic units to the units of meaning, such as words and sentences.

Erythropoietin-mediated IL-17 F attenuates sepsis-induced gut microbiota dysbiosis and barrier dysfunction.

Septic gut damage is critical in the progression of sepsis and multiple organ failure, characterized by gut microbiota dysbiosis and epithelium deficiency in the gut barrier. Recent studies highlight the protective effects of Erythropoietin (EPO) on multiple organs. The present study found that EPO treatment significantly alleviated the survival rate, suppressed inflammatory responses, and ameliorated intestine damage in mice with sepsis. EPO treatment also reversed sepsis-induced gut microbiota dysbiosis. The protective role of EPO in the gut barrier and microbiota was impaired after EPOR knockout. Notably, we innovatively demonstrated that IL-17 F screened by transcriptome sequencing could ameliorate sepsis and septic gut damage including gut microbiota dysbiosis and barrier dysfunction, which was verified by IL-17 F-treated fecal microbiota transplantation (FMT) as well. Our findings highlight the protection effects of EPO-mediated IL-17 F in sepsis-induced gut damage by alleviating gut barrier dysfunction and restoring gut microbiota dysbiosis. EPO and IL-17 F may be potential therapeutic targets in septic patients.

Maternal and perinatal outcomes of low-dose aspirin plus low-molecular-weight heparin therapy on antiphospholipid antibody-positive pregnant women with chronic hypertension.

Objectives: Positive antiphospholipid antibodies (aPLs) and chronic hypertension (CH) in pregnancy are important causes of maternal and neonatal morbidity and mortality. However, there are no relevant studies on the treatment of aPL-positive pregnant women with CH. This study aimed to determine the effect of low-dose aspirin (LDA) plus low-molecular-weight heparin (LMWH) on maternal and perinatal outcomes in persistently aPL-positive pregnant women with CH. Methods: This study was performed at the First Affiliated Hospital of Dalian Medical University in Liaoning, China, from January 2018 to December 2021. Pregnant women diagnosed CH and persistently positive aPL who had no autoimmune disease such as systemic lupus erythematosus, antiphospholipid syndrome were recruited and divided into control group (LDA and LWMH were not used), LDA group (LDA was used) and LDA plus LMWH group (both LDA and LMWH were used) according to whether they use LDA and/or LMWH. A total of 81 patients were enrolled, including 40 patients in the control group, 19 patients in the LDA group, and 22 patients in the LDA plus LMWH group. The maternal and perinatal outcomes of LDA plus LMWH therapy were analysed. Results: Compared with control group, the rate of severe preeclampsia in LDA group (65.00% vs. 31.58%, p = 0.016) and LDA plus LMWH group (65.00% vs. 36.36%, p = 0.030) had a statistically significant reduction. Compared with control group, the rate of fetal loss in LDA group (35.00% vs. 10.53%, p = 0.014) and LDA plus LMWH group (35.00% vs. 0.00%, p = 0.002) had a statistically significant reduction. Compared with control group, the rate of live birth in LDA group (65.00% vs. 89.74%, p = 0.048) and LDA plus LMWH group (65.00% vs. 100.00%, p = 0.002) had a statistically significant increased. Compared withcontrol group, the incidence of early-onset preeclampsia (47.50% vs. 36.84%, p = 0.008) and early-onset severe preeclampsia (47.50% vs. 13.64%, p = 0.001) in the LDA plus LMWH group decreased and were statistically different. Furthermore, we also found that LDA or LDA plus LMWH hadn't increase the rate of blood loss and placental abruption. Conclusion: Both LDA and LDA combined with LMWH could decrease the incidence of severe preeclampsia, decrease the rate of foetal loss, increase the rate of live birth. However, LDA plus LWMH could reduce and delay the onset of severe preeclampsia, prolong the gestational age and increase the rate of full-term delivery, improve the maternal and perinatal outcomes.

Achieving adjustable digital-to-analog conversion in memristors with embedded Cs2AgSbBr6 nanoparticles.

In this work, the proportions of Cs2AgSbBr6 nanoparticles (NPs) mixed in a PMMA film are adjusted to the digital and analog types of resistive switching (RS) behaviors in Ag/PMMA&Cs2AgSbBr6-NPs/ITO memristor devices. It is confirmed that when the concentration of NPs doped in the PMMA film is about 5 wt%, the memristor devices demonstrate bipolar digital RS behaviors with excellent electrical characteristics such as low operating voltage, high ON/OFF ratio (>500), good endurance (>800 cycles), and stable retention ability (>104 s). However, the devices showed a transition to analog-type memristive behavior when the concentration of NPs doped in the PMMA film is around 10 wt%, and several artificial synapse behaviors are successfully simulated. The device model simulation is also used to explore the effect of the NPs on the local electric field and growing filaments. Our work provides an opportunity to explore next-generation artificial synapse devices based on lead-free halide perovskites.

Low-Threshold, Multiple High-Order Harmonics Fiber Laser Employing Cr2Si2Te6 Saturable Absorber.

Abundant research findings have proved the value of two-dimensional (2D) materials in the study of nonlinear optics in fiber lasers. However, there remains two problems: how to reduce the start-up threshold, and how to improve the damage threshold, of fiber lasers based on 2D materials. A 15.1 mW low-threshold mode-locked fiber laser, based on a Cr2Si2Te6 saturable absorber (SA) prepared by the liquid-phase exfoliation method, is demonstrated successfully in this work. This provides a useful and economical method to produce SAs with low insertion loss and low saturation intensity. Besides, multiple high-order harmonics, from the fundamental frequency (12.6 MHz) to the 49th-order harmonic (617.6 MHz), mode-locked operations are recorded. The experimental results indicate the excellent potential of Cr2Si2Te6 as an optical modulator in exploring the soliton dynamics, harmonic mode locking, and other nonlinear effects in fiber lasers.

Severe fever with thrombocytopenia syndrome virus aerosol infection in C57/BL6 mice.

Although secondary cases have become infected with the SFTSV after being in the same space without direct contact with the index case, it has not been experimentally determined if the SFTSV can be transmitted through aerosols. Here, this study aimed to verify if the SFTSV could be transmitted by aerosols. Firstly, we demonstrated that the SFTSV can infect BEAS-2B cells, and SFTSV genomes can be isolate from mild patient's sputum, which provided a foundation for the existence of SFTSV aerosol transmission. Then, we evaluated total antibody production in serum and viral load in tissue of mice infected with SFTSV by aerosols. The results showed that the presence of antibodies is related to the dose of virus infection and the SFTSV preferentially replicates in the lungs of mice following an aerosol exposure. Our study will help update the prevention and treatment guidelines for SFTSV and prevent the spread of the SFTSV in hospitals.

Low-dimensional nanomaterials as an emerging platform for cancer diagnosis and therapy.

The burden of cancer is increasing, being widely recognized as one of the main reasons for deaths among humans. Despite the tremendous efforts that have been made worldwide to stem the progression and metastasis of cancer, morbidity and mortality in malignant tumors have been clearly rising and threatening human health. In recent years, nanomedicine has come to occupy an increasingly important position in precision oncotherapy, which improves the diagnosis, treatment, and long-term prognosis of cancer. In particular, LDNs with distinctive physicochemical capabilities have provided great potential for advanced biomedical applications, attributed to their large surface area, abundant surface binding sites, and good cellular permeation properties. In addition, LDNs can integrate CT/MR/US/PAI and PTT/PDT/CDT/NDDS into a multimodal theranostic nanoplatform, enabling targeted therapy and efficacy assessments for cancer. This review attempts to concisely summarize the classification and major properties of LDNs. Simultaneously, we particularly emphasize their applications in the imaging, diagnosis, and treatment of cancerous diseases.

Evaluating the efficacy of serological testing of clinical specimens collected from patients with suspected brucellosis.

BACKGROUND: This study aims to evaluate the efficacy of the standard agglutination test (SAT), the Brucellacapt test and enzyme-linked immunosorbent assay (ELISA) in clinical specimens collected from patients with suspected brucellosis. METHODS: A prospective study was conducted from December 2020 to December 2021. Brucellosis was diagnosed on the basis of clinical evidence, and confirmed by isolation of Brucella or a four-fold rise in SAT titer. All samples were tested by the SAT, ELISA and the Brucellacapt test. Titers ≥1:100 were considered as SAT positive; ELISA was considered positive when an index greater than 11 was detected, while titers ≥1/160 indicated positivity on the Brucellacapt test. The specificity, sensitivity, and positive (PPVs) and negative predictive values (NPVs) of the three different methods were calculated. RESULTS: A total of 149 samples were collected from patients with suspected brucellosis. The sensitivities for the SAT, IgG, and IgM detection were 74.42%, 88.37% and 74.42%, respectively. The specificities were 95.24%, 93.65%, and 88.89%, respectively. The simultaneous measurement of IgG and IgM improved the sensitivity (98.84%) but reduced the specificity (84.13%) compared to each antibody test separately. The Brucellacapt test had excellent specificity (100%) and a high PPV (100%); however, the sensitivity and NPV were 88.37% and 86.30%, respectively. The combination of IgG detection by ELISA and the Brucellacapt test had excellent diagnostic performance, with 98.84% sensitivity and 93.65% specificity. CONCLUSION: This study showed that the simultaneous performance of IgG detection by ELISA and the Brucellacapt test has the potential to overcome the current limitations of detection.

Monoterpenoid derivatives from Hyssopus cuspidatus Boriss. and their bioactivities.

Six undescribed monoterpenoids, together with twelve known compounds were isolated and identified from Hyssopus cuspidatus Boriss. Their structures were established by spectroscopic analysis, and the absolute configurations were established by ECD calculations and single-crystal X-ray diffraction crystallography. The isolated compounds were tested for their anti-inflammatory, antibacterial and antitumor activities. Most of the compounds showed potent anti-inflammatory activities. Among them, 3ß-hydroxy-7,8-dihydro-ß-ionone (8), oleanolic acid (17) and acetylpleamolic acid (18) showed strong anti-inflammatory activity against IL-6 and TNF-α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Several compounds showed moderate inhibitory activities against Staphylococcus aureus, Candida albicans, and Escherichia coli. And (4S)-p-menth-l-ene-7,8-diol 8-O-ß-D-glucopyranoside (16) showed antitumor activities against MCF-8 and HT-29 cell lines with IC50 values of 93.39 ± 3.69 and 71.89 ± 2.94 µM, respectively. Oleanolic acid (17) showed moderate antitumor activity against HT-29 cell lines with an IC50 value of 52.62 ± 1.63 µM. In this study, the discovery of anti-inflammatory, antibacterial and antitumor components from H. cuspidatus could benefit further development and utilization of this plant.

Loss of transketolase promotes the anti-diabetic role of brown adipose tissues.

Transketolase (TKT), an enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), bi-directionally regulates the carbon flux between the PPP and glycolysis. Loss of TKT in adipose tissues decreased glycolysis and increased lipolysis and uncoupling protein-1 (UCP1) expression, protecting mice from high-fat diet-induced obesity. However, the role of TKT in brown adipose tissue (BAT)-dependent glucose homeostasis under normal chow diet remains to be elucidated. We found that TKT ablation increased levels of glucose transporter 4 (GLUT4), promoting glucose uptake and glycogen accumulation in BAT. Using the streptozotocin (STZ)-induced diabetic mouse model, we discovered that enhanced glucose uptake due to TKT deficiency in BAT contributed to decreasing blood glucose and weight loss, protecting mice from STZ-induced diabetes. Mechanistically, TKT deficiency decreased the level of thioredoxin-interacting protein, a known inhibitor for GLUT4, by decreasing NADPH and glutathione levels and inducing oxidative stress in BAT. Therefore, our data reveal a new role of TKT in regulating the anti-diabetic function of BAT as well as glucose homeostasis.