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.

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.

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.

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.

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.

MEK1-dependent MondoA phosphorylation regulates glucose uptake in response to ketone bodies in colorectal cancer cells.

The Mondo family transcription factor MondoA plays a pivotal role in sensing metabolites, such as glucose, glutamine, and lactic acid, to regulate glucose metabolism and cell proliferation. Ketone bodies are important signals for reducing glucose uptake. However, it is unclear whether MondoA functions in ketone body-regulated glucose transport. Here we reported that ketone bodies promoted MondoA nuclear translocation and binding to the promoter of its target gene TXNIP. Ketone bodies reduced glucose uptake, increased apoptosis and decreased proliferation of colorectal cancer cells, which was impeded by MondoA knockdown. Moreover, we identified MEK1 as a novel component of the MondoA protein complex using a proteomic approach. Mechanistically, MEK1 interacted with MondoA and enhanced tyrosine 222, but not serine or threonine, phosphorylation of MondoA, inhibiting MondoA nuclear translocation and transcriptional activity. Ketone bodies decreased MEK1-dependent MondoA phosphorylation by blocking MondoA and MEK1 interaction, leading to MondoA nuclear translocation, TXNIP transcription, and inhibition of glucose uptake. Therefore, our study not only demonstrated that ketone bodies reduce glucose uptake, promote apoptosis, and inhibit cell proliferation in colorectal cancer cells by regulating MondoA phosphorylation but also identified MEK1-dependent phosphorylation as a new mechanism to manipulate MondoA activity.

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.

Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

OBJECTIVE: Over-proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of RA disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. METHODS: Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a CIA mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. RESULTS: Compared with healthy controls, ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1 (FTH1), GPX4 and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in healthy controls, the increase in antioxidation was slightly higher than oxidation. RNA-seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. CONCLUSIONS: In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease.

Fully Automatic Knee Joint Segmentation and Quantitative Analysis for Osteoarthritis from Magnetic Resonance (MR) Images Using a Deep Learning Model.

BACKGROUND We aimed to develop and evaluate a deep learning-based method for fully automatic segmentation of knee joint MR imaging and quantitative computation of knee osteoarthritis (OA)-related imaging biomarkers. MATERIAL AND METHODS This retrospective study included 843 volumes of proton density-weighted fat suppression MR imaging. A convolutional neural network segmentation method with multiclass gradient harmonized Dice loss was trained and evaluated on 500 and 137 volumes, respectively. To assess potential morphologic biomarkers for OA, the volumes and thickness of cartilage and meniscus, and minimal joint space width (mJSW) were automatically computed and compared between 128 OA and 162 control data. RESULTS The CNN segmentation model produced reasonably high Dice coefficients, ranging from 0.948 to 0.974 for knee bone compartments, 0.717 to 0.809 for cartilage, and 0.846 for both lateral and medial menisci. The OA-related biomarkers computed from automatic knee segmentation achieved strong correlation with those from manual segmentation: average intraclass correlations of 0.916, 0.899, and 0.876 for volume and thickness of cartilage, meniscus, and mJSW, respectively. Volume and thickness measurements of cartilage and mJSW were strongly correlated with knee OA progression. CONCLUSIONS We present a fully automatic CNN-based knee segmentation system for fast and accurate evaluation of knee joint images, and OA-related biomarkers such as cartilage thickness and mJSW were reliably computed and visualized in 3D. The results show that the CNN model can serve as an assistant tool for radiologists and orthopedic surgeons in clinical practice and basic research.

Soliton phenomena in normal and anomalous dispersion regions in Er-doped mode-locked fiber lasers based on Cr2Si2Te6 saturable absorbers.

Investigations of optical solitons have always been a hot topic due to their important scientific research value. In recent years, ultrafast lasers based on two-dimensional materials such as saturable absorbers (SAs) have become the focus of optical soliton research. In this work, various soliton operations are demonstrated in Er-doped fiber lasers (EDFLs) based on ${{\rm Cr}_2}{{\rm Si}_2}{{\rm Te}_6}$ SAs. First, a low-threshold passively mode-locked EDFL with traditional soliton output is constructed, and the pump threshold is as low as 10.1 mW. Second, by adjusting the net dispersion of the cavity, stable dissipative soliton operation can also be obtained. Traditional soliton mode-locked operation with controllable Kelly sidebands from first order to fourth order is realized by adjusting the pump power in a double-ended pumped structure, and the SNR is as high as 55 dB. All results prove that ${{\rm Cr}_2}{{\rm Si}_2}{{\rm Te}_6}$ used as SA material has great potential and wide application prospects in investigating optical soliton operations in mode-locked fiber lasers with both normal and anomalous dispersion.

Third-order harmonic mode-locked and Q-switched Er-doped fiber laser based on a Cr2Ge2Te6 saturable absorber.

This paper reports the generation of fundamental solitons and third-order solitons in an erbium-doped fiber laser (EDFL) by a Cr2Ge2Te6-polyvinyl alcohol (CGT-PVA) saturable absorber (SA). Stable fundamental solitons at 1559.09 nm at a repetition frequency of 5.1 MHz were detected, and third-order solitons with a maximum output power of 6.807 mW and narrowest monopulse duration of 615.2 fs were obtained under a repetition frequency of 15.3 MHz by changing pump power. To the best of our knowledge, it is the first time to achieve a Q-switched pulse with a minimum pulse duration of 2.2 µs and maximum single pulse energy of 12.11 nJ in EDFL based on CGT-PVA SA after reducing the cavity length. Its repetition rate monotonically increased from 18.8 kHz to 61.8 kHz with a tuning range of about 43 kHz. The experimental results sufficiently demonstrate that CGT has enormous potential as an ultrafast photonics device.

Confirmation of Rickettsia conorii Subspecies indica Infection by Next-Generation Sequencing, Shandong, China.

We describe 3 similar cases of rickettsial disease that occurred after tick bites in a mountainous rural area of Shandong Province, China. Next-generation sequencing indicated the etiologic agent of 1 patient was Rickettsia conorii subspecies indica. This agent may be more widely distributed across China than previously thought.

Subarachnoid hemorrhage secondary to Brucella-induced cerebral aneurysm: a case report.

BACKGROUND: Brucellosis is a common zoonotic disease that is prevalent in many areas worldwide. This infectious disease can occasionally affect the central nervous system but intracranial arteries are rarely involved. CASE PRESENTATION: A 17-year-old female who had a history of recurrent fever for 1 month was admitted for subarachnoid hemorrhage due to cerebral aneurysm rupture. Surgery was performed to fix the aneurysm, but the patient had persistent fever after the surgery. Cerebrospinal fluid testing showed a high white blood cell count and elevated protein level but no pathogen was identified in the first two tests. Brucella melitensis was identified in the third cerebrospinal fluid culture, and a diagnosis of brucellosis was finally rendered. The patient was subsequently treated with anti-Brucella medications and her symptoms improved significantly at the last follow-up. CONCLUSION: Although extremely rare, Brucella-induced cerebral aneurysms can occur and this should be considered in the differential diagnosis of cerebrovascular accidents, especially in Brucella epidemic areas.

Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid.

As a natural phenolic acid product of plant source, caffeic acid displays diverse biological activities and acts as an important precursor for the synthesis of other valuable compounds. Limitations in chemical synthesis or plant extraction of caffeic acid trigger interest in its microbial biosynthesis. Recently, Saccharomyces cerevisiae has been reported for the biosynthesis of caffeic acid via episomal plasmid-mediated expression of pathway genes. However, the production was far from satisfactory and even relied on the addition of precursor. In this study, we first established a controllable and stable caffeic acid pathway by employing a modified GAL regulatory system to control the genome-integrated pathway genes in S. cerevisiae and realized biosynthesis of 222.7 mg/L caffeic acid. Combinatorial engineering strategies including eliminating the tyrosine-induced feedback inhibition, deleting genes involved in competing pathways, and overexpressing rate-limiting enzymes led to about 2.6-fold improvement in the caffeic acid production, reaching up to 569.0 mg/L in shake-flask cultures. To our knowledge, this is the highest ever reported titer of caffeic acid synthesized by engineered yeast. This work showed the prospect for microbial biosynthesis of caffeic acid and laid the foundation for constructing biosynthetic pathways of its derived metabolites. KEY POINTS: Genomic integration of ORgTAL, OHpaB, and HpaC for caffeic acid production in yeast. Feedback inhibition elimination and Aro10 deletion improved caffeic acid production. The highest ever reported titer (569.0 mg/L) of caffeic acid synthesized by yeast.

Improved Stability and Photothermal Performance of Polydopamine-Modified Fe3 O4 Nanocomposites for Highly Efficient Magnetic Resonance Imaging-Guided Photothermal Therapy.

Magnetic nanomaterials are a promising class of contrast agents for magnetic resonance imaging (MRI). However, their poor stability and low relaxivity are major challenges hindering their clinical applications. In this study, magnetic theranostic nanoagents based on polydopamine-modified Fe3 O4 (Fe3 O4 @PDA) nanocomposites are fabricated for MRI-guided photothermal therapy (PTT) cancer treatments. Their high transverse relaxivity of 337.8 mM-1 s-1 makes these Fe3 O4 @PDA nanocomposites a promising T2 -weighted MRI contrast agent for cancer diagnosis and image-guided cancer therapy. Due to the good photothermal effect of polydopamine (PDA), the tumors of 4T1 tumor-bearing mice are completely excised by PTT. Most importantly, the PDA shell also improves the stability of the Fe3 O4 @PDA nanocomposites, which contributes to their excellent, long-term performance in MRI and PTT applications. Their good stability, high T2 relaxivity, robust biocompatibility, and satisfactory treatment effect give these Fe3 O4 @PDA nanocomposites great potential for use in cancer theranostics.

Improved Early Detection of Focal Brucellosis Complications with Anti-Brucella IgG.

To evaluate the associations of inflammatory factors and serological test results with complicated brucellosis, we recruited 285 patients with a diagnosis of brucellosis between May 2016 and September 2019. The patients were subsequently classified into two groups according to the presence of complications. We collected demographic and clinical information and routine laboratory test results in addition to anti-Brucella IgG and IgM levels. Anti-Brucella IgG and IgM were uniformly tested using enzyme-linked immunosorbent assays (ELISAs) in this study. Among the 285 patients with brucellosis, 111 (38.95%) had complicated brucellosis. Osteoarthritis occurred more often in the subacute and chronic stages than in the acute stage (P = 0.002). Genital infection occurred more frequently in the acute stage than in the other stages (P = 0.023). Fever was not frequently observed in complicated cases (P < 0.001). The erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) and anti-Brucella IgM and IgG levels were higher in complicated-brucellosis patients than in uncomplicated-brucellosis patients (P < 0.001). Anti-Brucella IgG, with an area under the curve of 0.885 (95% confidence interval [CI], 0.847 to 0.924), was the most robust indicator of complicated brucellosis. Positive culture, anti-Brucella IgM, the ESR, and CRP could be considered indicators, but their efficacy was weaker than that of IgG. In conclusion, a high ESR, high CRP, high anti-Brucella IgM and IgG levels, and positive culture were indicators of complicated brucellosis; among these, anti-Brucella IgG was the most robust biomarker.

Hybrid Lead Iodide Perovskites with Mixed Cations of Thiourea and Methylamine, From One Dimension to Three Dimensions.

Hybrid halide perovskites featuring as new materials of high-performance solar cells have attracted great research interest. The temperature-dependent dimensional transition of halide perovskites is a crucial handle in the preparation of perovskite films. Only the small cations of methylammonium (MA) or formamidinium (FA) have been involved for most of the dimensional transition materials. In this work, thiourea (tu) is introduced into hybrid halide materials. A new series of 1D ribbonlike hybrid lead iodides with tu and MA cations are reported that were crystallographically characterized as MAn(Htu)n+1PbnI4n+1 (n = 1-4 denoted as 1-4, respectively; in 1, MA is replaced by tu). The width of the perovskite ribbon increases from one PbI6 octahedron to four corner-fused octahedra. Compounds 2 and 3 can be turned into a black 3D perovskite after annealing. This is an unusual mixed MA-tu hybrid halide perovskite system, in which the tu molecule plays an important role in manipulating the dimensions and their photoconductive properties. Scanning electron microscopy of the blackened sample shows that there are a lot of regular vent holes on the smooth crystal surface with sizes of hundreds of nanometers. The tunable structures and porous crystals might be advantageous in the sense of material modulation.

ELISA is superior to bacterial culture and agglutination test in the diagnosis of brucellosis in an endemic area in China.

BACKGROUND: Brucellosis is endemic in many areas in China. The current diagnosis of Brucellosis predominantly relies on the traditional bacterial culture and serum agglutination test. In this study, we aimed to explore the value of ELISA in the diagnosis of Brucellosis in Chinese population. METHODS: We recruited 235 patients with a diagnosis of Brucellosis at different clinical stages: 117 in acute, 78 in subacute, and 40 in chronic. We also recruited 248 control patients who presented with similar clinical symptoms but with a different diagnosis other than Brucellosis. In addition, 90 healthy volunteers were also recruited. Bacterial culture, agglutination test and ELISA assay were performed to detect Brucella spp. RESULTS: Among 235 patients with Brucellosis, 51 (21.7%) was positive for bacterial culture, 150 (63.8%) were positive by agglutination test, and 232 (98.7%) were positive by ELISA (IgG and/or IgM). When we stratified the patients based on the disease stages (acute, subacute and chronic), ELISA was the most sensitive method and showed a highest positive rate in all stages. By Receiver Operating Characteristic Curve analysis of ELISA results, we found that measurement of IgG level was superior to measurement of IgM level (AUC, 0.993 versus 0.877). Since the measurement of IgG itself missed rare cases in acute phase, we recommended measuring IgG and IgM simultaneously by ELISA for the diagnosis of Brucellosis. In term of the specificity of ELISA in the diagnosis of Brucellosis, our study showed that only 1.6% (4/248) non-Brucellosis patients were positive by ELISA; all positive cases were IgM only and none showed positive IgG. Similar results were found in healthy volunteers. In summary, our study concluded that ELISA is the most sensitive and specific method to detect Brucellosis in Chinese population. CONCLUSIONS: ELISA assay is sensitive, fast, and convenient to detect Brucellosis. It shows the high sensitivity and specifity and should be used as a routine lab test when Brucellosis is suspected in clinical practice.

Increased world knowledge in older adults does not prevent decline in world knowledge comprehension: An ERP study.

A meaningful sentence might not be sensible according to world knowledge. In aging, world knowledge continues to increase, but semantic processing declines. An intriguing question is whether increased world knowledge aids world knowledge comprehension, even in the face of declining semantic processing. The present study collected EEG data from 43 older and 43 younger adults as they read correct sentences, sentences with a semantic violation, and sentences with a world knowledge violation. Compared to younger adults, older adults had a significantly greater reduction in amplitude and delayed peak/onset latency of N400 for both semantic and world knowledge integration. A significant Group by Condition by Region interaction revealed that, although the N400 amplitude under the semantic violation condition was comparable to that under the world knowledge violation condition in younger adults, the N400 amplitude in the posterior brain region was significantly smaller under the world knowledge violation condition than under the semantic violation condition in older adults. The N400 difference between world knowledge and semantic violation conditions was negatively correlated only with vocabulary scores. In conclusion, age-related increases in world knowledge do not help older adults to comprehend world knowledge more effectively.

Nonlinear optical characteristics of ZrSe2 and its application for designing multi-wavelength mode-locked operations.

In our work, a ZrSe2-polyvinyl alcohol film-type saturable absorber (SA) with a modulation depth of 4.99% and a saturable intensity of 12.42MW/cm2 was successfully prepared and employed in mode-locked Er-doped fiber laser. The fiber laser can generate stable multi-wavelength mode-locked operations with a threshold power of 224 mW and a maximum average output power of 3.272 mW at the repetition rate of 3.38 MHz for the first time, to the best of our knowledge. Our experimental results fully prove that ZrSe2 nanosheets were efficient SA candidates for demonstrating multi-wavelength mode-locked operation fiber lasers due to their tunable absorption peak and excellent saturable absorption properties.