IL-1ß-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance.

Interleukin-1ß (IL-1ß) is a key protein in inflammation and contributes to tumor progression. However, the role of IL-1ß in cancer is ambiguous or even contradictory. Here, we found that upon IL-1ß stimulation, nicotinamide nucleotide transhydrogenase (NNT) in cancer cells is acetylated at lysine (K) 1042 (NNT K1042ac) and thereby induces the mitochondrial translocation of p300/CBP-associated factor (PCAF). This acetylation enhances NNT activity by increasing the binding affinity of NNT for NADP+ and therefore boosts NADPH production, which subsequently sustains sufficient iron-sulfur cluster maintenance and protects tumor cells from ferroptosis. Abrogating NNT K1042ac dramatically attenuates IL-1ß-promoted tumor immune evasion and synergizes with PD-1 blockade. In addition, NNT K1042ac is associated with IL-1ß expression and the prognosis of human gastric cancer. Our findings demonstrate a mechanism of IL-1ß-promoted tumor immune evasion, implicating the therapeutic potential of disrupting the link between IL-1ß and tumor cells by inhibiting NNT acetylation.

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes.

BACKGROUND: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. RESULT: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. CONCLUSION: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Phosphate promotes Arabidopsis root skewing and circumnutation through reorganisation of the microtubule cytoskeleton.

Phosphate (Pi) plays a key role in plant growth and development. Hence, plants display a range of adaptations to acquire it, including changes in root system architecture (RSA). Whether Pi triggers directional root growth is unknown. We investigated whether Arabidopsis roots sense Pi and grow towards it, that is whether they exhibit phosphotropism. While roots did exhibit a clear Pi-specific directional growth response, it was, however, always to the left, independent of the direction of the Pi gradient. We discovered that increasing concentrations of KH2PO4, trigger a dose-dependent skewing response, in both primary and lateral roots. This phenomenon is Pi-specific - other nutrients do not trigger this - and involves the reorganisation of the microtubule cytoskeleton in epidermal cells of the root elongation zone. Higher Pi levels promote left-handed cell file rotation that results in right-handed, clockwise, root growth and leftward skewing as a result of the helical movement of roots (circumnutation). Our results shed new light on the role of Pi in root growth, and may provide novel insights for crop breeding to optimise RSA and P-use efficiency.

Augmented reality system based on the integration of polarization-independent metalens and micro-LEDs.

Augmented reality (AR), a technology that superimposes virtual information onto a user's direct view of real-world scenes, is considered one of the next-generation display technologies and has been attracting considerable attention. Here, we propose a flat optic AR system that synergistically integrates a polarization-independent metalens with micro light-emitting diodes (LEDs). A key component is a meticulously designed metalens with a numerical aperture of 0.25, providing a simulated focusing efficiency of approximately 76.5% at a wavelength of 532 nm. Furthermore, the laser measurement system substantiates that the fabricated metalens achieves a focusing efficiency of 70.8%. By exploiting the reversibility of light characteristics, the metalens transforms the divergent light from green micro-LEDs into a collimated beam that passes through the pupil and images on the retina. Monochromatic pixels with a size of 5×5 µm2 and a pitch of 10 µm can be distinctly resolved with a power efficiency of 50%. This work illustrates the feasibility of integrating the metalens with microdisplays, realizing a high-efficiency AR device without the need for additional optical components and showcasing great potential for the development of near-eye display applications.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

FNDC5/Irisin protects neurons through Caspase3 and Bax pathways.

Irisin is a glycosylated protein formed from the hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have demonstrated that FNDC5/Irisin is involved in the regulation of glucose and lipid metabolism, it can inhibit inflammation and have neuroprotective effects. However, the effect and mechanism of FNDC5/Irisin on motor neuron-like cell lines (NSC-34) have not been reported. In this study, we used lipopolysaccharide to construct cellular oxidative stress injury models and investigated the potential roles of FNDC5/Irisin on neurons by different cellular and molecular pathways. Taken together, our findings showed that FNDC5/Irisin can protect neurons, and this effect might be associated with Caspase3 and Bax pathways. These results laid the foundation for neuronal protection and clinical translation of FNDC5/Irisin therapy.

Exercise Therapy Research in Ankylosing Spondylitis-Induced Back Pain: A Bibliometric Study (2004-2023).

BACKGROUND Ankylosing spondylitis (AS), a chronic inflammatory disease predominantly causing back pain, affects up to 0.5% of the global population, more commonly in males. Frequently undiagnosed in early stages, AS is often associated with comorbid depression and anxiety, imposing significant healthcare burdens. Despite available pharmaceutical treatments, exercise therapy (ET) has emerged as an effective, side-effect-free alternative, particularly for managing AS-induced back pain. This study aims to explore the research trends in ET for treating AS back pain from 2004-2023. MATERIAL AND METHODS A comprehensive analysis of 437 articles, sourced from the Science Citation Index-Expanded within the Web of Science Core Collection, was conducted using CiteSpace 6.2.R5. This study spanned from 2004 to October 15, 2023, examining publications, authors, institutions, and keywords to assess keyword co-occurrences, temporal progressions, and citation bursts. RESULTS Research interest in ET for AS began escalating around 2008 and has since shown steady growth. The USA emerged as a significant contributor, with Van der Heijde, Desiree, and RUDWALEIT M being notable authors. Key institutions include Assistance Publique Hopitaux Paris and UDICE-French Research Universities, with ANN RHEUM DIS being the most influential journal. The field's evolution is marked by interdisciplinary integration and branching into various sub-disciplines. CONCLUSIONS Exercise therapy for AS-induced back pain is a growing research area, necessitating further exploration in clinical management and rehabilitation strategies. The relationship between ET and osteoimmunological mechanisms remains a focal point for future research, with a trend towards personalized and interdisciplinary treatment approaches.

Nine New Antibacterial Diterpenes and Steroids from the South China Sea Soft Coral Lobophytum catalai Tixier-Durivault.

Five new cembrane-type diterpenes, lobocalines A-E (1-5), and four new steroids, lobocaloids A-D (9-12), along with six known related compounds (6-8 and 13-15) were isolated from the Yalong Bay soft coral Lobophytum catalai Tixier-Durivault. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses and comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 8-12 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa.

Assessing the Clinical Effectiveness of an Exergame-Based Exercise Training Program Using Ring Fit Adventure to Prevent and Postpone Frailty and Sarcopenia Among Older Adults in Rural Long-Term Care Facilities: Randomized Controlled Trial.

BACKGROUND: Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. OBJECTIVE: We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. METHODS: This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. RESULTS: We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). CONCLUSIONS: The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fmed.2022.1071409.

Accelerating pandemic response with the emergency Omicron RT-PCR test: A comprehensive solution for COVID-19 diagnosis and tracking.

The Omicron variant of concern (VOC) has surged in many countries and replaced the previously reported VOC. To identify different Omicron strains/sublineages on a rapid, convenient, and precise platform, we report a novel multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) method in one tube based on the Omicron lineage sequence variants' information. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subvariants were used in a PCR-based assay for rapid identification of Omicron sublineage genotyping in 1000 clinical samples. Several characteristic mutations were analyzed using specific primers and probes for the spike gene, del69-70, and F486V. To distinguish Omicron sublineages (BA.2, BA.4, and BA.5), the NSP1:141-143del in the ORF1a region and D3N mutation in membrane protein occurring outside the spike protein region were analyzed. Results from the real-time PCR assay for one-tube accuracy were compared to those of whole genome sequencing. The developed PCR assay was used to analyze 400 SARS-CoV-2 positive samples. Ten samples determined as BA.4 were positive for NSP1:141-143del, del69-70, and F486V mutations; 160 BA.5 samples were positive for D3N, del69-70, and F486V mutations, and 230 BA.2 samples were without del69-70. Screening these samples allowed the identification of epidemic trends at different time intervals. Our novel one-tube multiplex PCR assay was effective in identifying Omicron sublineages.

Knockdown of circ-PIP5K1A overcomes resistance to cisplatin in ovarian cancer by miR-942-5p/NFIB axis.

Cisplatin (DDP)-based chemotherapy is the main chemotherapeutic agent for ovarian cancer (OC) treatment. Circular RNA PIP5K1A (circ-PIP5K1A) was found to promote OC tumorigenesis. However, whether circ-PIP5K1A was involved in DDP resistance in OC remains unclear. Levels of circ-PIP5K1A, microRNA (miR)-942-5p, and nuclear factor I B (NFIB) were detected using quantitative real-time PCR and Western blot assays. In-vitro experiments were conducted by using cell counting kit-8, cell colony formation, 5-ethynyl-2'-deoxyuridine, flow cytometry, and transwell assays, respectively. In-vivo assay was performed using murine xenograft model. The binding interaction between miR-942-5p and circ-PIP5K1A or NFIB was confirmed using dual-luciferase reporter assay. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy and Western blot. Circ-PIP5K1A was highly expressed in DDP-resistant OC tissues and cells. Circ-PIP5K1A knockdown could constrain the proliferation, migration, and invasion, as well as increase apoptosis and sensitivity to DDP in DDP-resistant OC cells. Mechanistically, circ-PIP5K1A acted as a sponge for miR-942-5p to positively regulate NFIB expression. Moreover, rescue experiments demonstrated that the anticancer and DDP sensitization effects caused by circ-PIP5K1A silencing in DDP-resistant OC cells were achieved through the miR-942-5p/NFIB axis. Importantly, circ-PIP5K1A silencing enhanced DDP efficacy and impeded tumor growth in OC in vivo . Additionally, we also found that circ-PIP5K1A was packaged into exosomes and could be internalized by surrounding cells. Circ-PIP5K1A knockdown reduced the resistance to DDP in OC via regulating miR-942-5p/NFIB axis. Besides that, circ-PIP5K1A was packaged into exosomes and exosomal circ-SKA3 could mediate intercellular communication between OC cells. These findings provided a promising therapeutic target for OC.

The positive effects of postbiotic (SWF concentration®) supplemented diet on skin mucus, liver, gut health, the structure and function of gut microbiota of common carp (Cyprinus carpio) fed with high-fat diet.

Postbiotics are an emerging research interest in recent years, which shows that metabolites, lysate extracts, cell wall components and even culture supernatants of probiotics can also exhibit significant prebiotic effects. In this study postbiotic stress worry free concentration® (SWFC) were prepared from the composition of culture supernatant of Cetobacterium somerae and Lactococcus lactis. The positive effects of SWFC supplemented diets on the growth performance, skin mucus, liver and gut health, and intestinal microbiota profile of Cyprinus carpio fed with high fat diets were investigated. 180 C. carpio with an average body weight of (3.01 ± 0.01) g were selected and randomly divided into three groups. They were fed with one of the three experimental diets supplemented with SWFC of 0 (control), 0.2 and 0.3 g/kg for 98 days, afterwards indexes were detected. The results revealed that, addition of SWFC had no significant effect on growth performance of C. carpio, while it can improve the health of the fish remarkably. In addition, SWFC improved mucosal C3, T-AOC, SOD activities, and decreased lipid peroxidation product MDA level, which were notably better than those in the control group (P < 0.05). In terms of the liver health systems, C. carpio fed on the diet supplemented with 0.2 g/kg of SWFC, showed significant improvement of the liver injured by HFD and reduce the contents of serum ALT and AST, and liver TAG (P < 0.05; P < 0.01). The expression of inflammation-related and lipid synthesis genes revealed that SWFC0.2 group could noteworthy enhance antioxidant capacity, reduced the expression of pro-inflammatory factors (TNF-α, IL-1ß) and lipid synthesis genes (ACC, FAS, PPAR-ß, PPAR-γ), and up-regulated the expression of anti-inflammatory factors (TGF-ß). Additionally, intestinal morphology arose inflammatory cell infiltration, while intestinal integrity was better in SWFC groups compared with the control. Furthermore, the contents of serum LPS and LBP were remarkably lower in the SWFC0.2 group compared with the control (P < 0.01). The mRNA expression of genes related to gut health indicated that SWFC supplementation noteworthy up-regulated the expression of antioxidant (Nrf2, CAT, GPX), immune (Hepcidin, IL-10) and tight junction protein-related (ZO-1, Occludin). Simultaneously, the results of GF-zebrafish showed that the relative expression of anti-inflammatory genes (IL-1ß, TGF-ß) and antioxidant related genes (Nrf2, HO-1) were significantly up-regulated in SWFC groups. Data on intestinal microbiota profile verified that, at the phylum level, the abundance of Fusobacteria was remarkably elevated in the SWFC groups (P < 0.05), whereas the abundance of Firmicutes was declined noteworthy in SWFC0.2 and SWFC0.3 compared to the control group (P < 0.05; P < 0.01) respectively. At the genus level, the abundance of Cetobacterium in the SWFC groups were notably higher than those in the control group (P < 0.05), while the Vibrio content in the SWFC groups was significantly decreased (P < 0.05). PCoA result indicated that the intestinal microflora of SWFC0.2 group was abundant and diverse. Our results elucidate that dietary supplementation of SWFC protects C. carpio from HFD induced inflammatory response and oxidative stress, ameliorate skin mucus, liver and gut health, and improve the gut microbiota balance. Therefore, SWFC could be considered as an improving-fish-health additive, when supplemented to aquatic animal feed. With regards to how SWFC regulates the immunity and inflammatory responses and which signal transductions are involved remains unclear and more scientific evidences are needed to address these issues.

Effect of intermolecular interaction of the charge-transfer complex between molecular "tweezers" and C60/C70 on second-order nonlinear optical properties.

To enhance understanding of the correlation between the intermolecular interaction and second-order nonlinear optical (NLO) properties, we studied a "molecular tweezer" with two corannulene substituents linked by a tetrahydro[5]helicene imide, which enabled highly sensitive and selective complexation of C60/C70 through convex-concave π-π interactions. The geometric structure, molecular orbitals, intermolecular interactions, electron absorption spectra and second-order NLO properties of the charge-transfer (CT) complexes formed by molecular tweezers and C60/C70 were studied by density functional theory. Larger fullerenes helped to increase the intermolecular interaction and CT, thereby increasing the first hyperpolarizabilities of CT complexes. Embedding of lithium ions helped to enhance the electron-absorption ability of fullerenes, thereby increasing the intermolecular interaction and intermolecular CT and, thus, enhancing their first hyperpolarizability significantly. Our data indicated that, through structure adjustment (including increasing the volume of fullerene and embedding alkali metal ions), we could enhance intermolecular interactions and improve intermolecular CT significantly. These actions could improve the second-order NLO properties of CT complexes.

Evaluation of diffuse glioma grade and proliferation activity by different diffusion-weighted-imaging models including diffusion kurtosis imaging (DKI) and mean apparent propagator (MAP) MRI.

PURPOSE: To evaluate two advanced diffusion models, diffusion kurtosis imaging and the newly proposed mean apparent propagation factor-magnetic resonance imaging, in the grading of gliomas and the assessing of their proliferative activity. METHODS: Fifty-nine patients with clinically diagnosed and pathologically proven gliomas were enrolled in this retrospective study. All patients underwent DKI and MAP-MRI scans. Manually outline the ROI of the tumour parenchyma. After delineation, the imaging parameters were extracted using only the data from within the ROI including mean diffusion kurtosis (MK), return-to-origin probability (RTOP), Q-space inverse variance (QIV) and non-Gaussian index (NG), and the differences in each parameter in the classification of glioma were compared. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of these parameters. RESULTS: MK, NG, RTOP and QIV were significantly different amongst the different grades of glioma. MK, NG and RTOP had excellent diagnostic value in differentiating high-grade from low-grade glioma, with largest areas under the curve (AUCs; 0.929, 0.933 and 0.819, respectively; P < 0.01). MK and NG had the largest AUCs (0.912 and 0.904) when differentiating grade II tumours from III tumours (P < 0.01) and large AUCs (0.791 and 0.786) when differentiating grade III from grade IV tumours. Correlation analysis of tumour proliferation activity showed that MK, NG and QIV were strongly correlated with the Ki-67 LI (P < 0.001). CONCLUSION: MK, RTOP and NG can effectively represent the microstructure of these altered tumours. Multimodal diffusion-weighted imaging is valuable for the preoperative evaluation of glioma grade and tumour proliferative activity.

Physical and psychosocial characteristics differ between individuals with knee pain and different knee osteoarthritis diagnostic criteria.

PURPOSE: Knee pain and osteoarthritis (OA) are common and often lead to disability among older adults. Existing published evidence, however, utilizes differing criteria to define studies' knee OA populations. We, therefore, aimed to determine whether differences exist in the characteristics of individuals with the presence of knee pain and different diagnostic criteria for knee OA. METHODS: The Promoting Independence in Seniors with Arthritis (PISA) study is a longitudinal observational study of individuals with and without knee pain and knee OA recruited from the orthopaedics clinic of the Universiti Malaya Medical Centre and the local hospital catchment. Patients were diagnosed with OA based on the American College of Rheumatology (ACR) criteria, the presence of knee pain, and a history of physician-diagnosed knee OA. Psychosocial parameters were measured using validated measures for social participation, independence, and ability to perform activities of daily living, and life satisfaction. RESULTS: Of the 230 included participants, mean age was 66.9 years (standard deviation: 7.2) and 166 (72.2%) were women. Kappa agreement between ACR criteria and knee pain was 0.525 and for ACR and physician-diagnosed OA it was 0.325. Binomial logistic regression analysis showed that weight, anxiety, and handgrip strength (HGS) were predictive of ACR OA. Knee pain was only predicted by HGS but not weight and anxiety. Physician-diagnosed OA was predicted by weight and HGS but not anxiety. HGS was predictive of ACR OA, knee pain, and physician-diagnosed OA. CONCLUSION: Our study showed that the characteristics of patients with OA are different, physically and psychosocially, depending on the criteria used. Poor agreement was observed between radiological diagnosis and the other diagnostic criteria. Our findings have important implications for the interpretation and comparison of published studies using different OA criteria.

The impact of the COVID-19 pandemic on emergency care of acute myocardial infarction: findings from the Taiwan Clinical Performance Indicator.

Acute myocardial infarction (AMI) treatment requires timely diagnosis and treatment for optimal health outcomes. The Coronavirus Disease (COVID-19) pandemic has caused changes in health-care delivery and utilization; therefore, the present study explored the changes in emergency care quality indicators for patients with AMI before and during different periods of government response to the COVID-19 outbreak in Taiwan. The Taiwan Clinical Performance Indicators database was used to evaluate the impact of COVID-19 on acute care quality indicators for patients with AMI during four periods: before the COVID-19 outbreak (Period I-1 January to 31 December 2019) and during three periods in which the central government imposed different levels of epidemic prevention and response alerts (Period II-1 January 2020 to 30 April 2021; Period III-1 May to 31 July 2021; and Period IV-1 August to 31 December 2021). A 15.9% decrease in monthly emergency department admission for patients with AMI occurred during Period III. The hospital 'door-to-electrocardiogram time being <10 min' indicator attainment was significantly lower during Periods III and IV. The attainment of 'dual antiplatelet therapy received within 6 hr of emergency department arrival' indicator improved in Period IV, whereas 'the primary percutaneous coronary intervention being received within 90 min of hospital arrival' indicator significantly decreased during Periods III and IV. The indicator 'in-hospital mortality' was unchanged within the study duration. Overall, the quality of care for patients with AMI was mildly influenced during the assessed pandemic periods, especially in terms of door-to-electrocardiogram time of <10 min and primary percutaneous coronary intervention received within 90 min of hospital arrival (Period III). Using our study results, hospitals can develop strategies regarding care delivery for patients with AMI during a COVID-19 outbreak on the basis of central government alert levels, even during the height of the pandemic.

Effect of Dapagliflozin on Ventricular Remodeling and Prognosis in Patients with Coronary Atherosclerotic Heart Disease Undergoing Percutaneous Coronary Intervention.

Objective: Acute coronary syndrome (ACS) is a common cardiovascular complication in patients with type 2 diabetes mellitus (T2DM) and significantly increases the risk of disability and death in T2DM patients. Dapagliflozin inhibits blood glucose reabsorption, improves insulin resistance, and reduces the occurrence of long-term adverse cardiovascular events, indicating the importance of Dapagliflozin as a drug for type 2 diabetes patients and its close relationship with coronary atherosclerotic heart disease. At present, there are few studies on the effects of Dapagliflozin intervention on ventricular remodeling and myocardial microperfusion in patients with ACS combined with T2DM after PCI. Methods: Between January 2019 and August 2023, a total of 35 patients diagnosed with Coronary atherosclerotic heart disease and T2DM were chosen as the observation group using a multi-stage cluster sampling method. Concurrently, 35 patients with similar age, height, weight, and healthy physical examination results were selected as the control group during the same time frame. We collected demographic data, symptoms and underlying diseases of the two groups Before enrollment and 6 months after discharge and compared the data between the two groups. Subsequently, multivariate logistic regression analysis was employed to identify indicators with statistically significant differences and to summarize the potential risk factors that could impact ventricular remodeling in patients with Coronary atherosclerotic heart disease and T2DM. Results: There was significant difference in LDL-C between the two groups, and the difference was statistically significant (P < .05). After treatment, the levels of hs-CRP, FBG, HbAlc and IL-6 in both groups were significantly decreased, and the decrease was more obvious in the observation group, with statistical significance (P < .05). These results indicated that Dapagliflozin intervention could significantly inhibit postoperative inflammation in patients with ACS combined with T2DM after PCI. LVMI of Observation group patients was significantly higher than Comparison group, LVEDD and ESVI of Observation group patients were significantly lower than Comparison group. The difference was statistically significant (P < .05). These results indicated that Dapagliflozin intervention could significantly inhibit the improvement of blood glucose index, ventricular remodeling and myocardial microperfusion in patients with ACS combined with T2DM after PCI. After treatment, TIMI Flow Count Frame Count (CTFC) level and Myocardial Perfusion (TMPG) level in the observation group were significantly lower than those in the comparison group, and the difference was statistically significant (P < .05). These results indicated that Dapagliflozin intervention could significantly inhibit ventricular remodeling and improve myocardial microperfusion in patients with ACS combined with T2DM after PCI. Conclusion: Dapagliflozin intervention can significantly inhibit inflammatory indexes in patients with Coronary atherosclerotic heart disease combined with T2DM after PCI, promote the improvement of blood glucose indexes, ventricular remodeling and myocardial microperfusion, and reduce the risk of occurrence.

Oxygenated Cembrane Diterpenes from the South China Sea Soft Coral Sinularia tumulosa.

The chemical investigation of the rarely studied soft coral Sinularia tumulosa resulted in the discovery of five oxygenated cembrane diterpenes 1-5, including two new compounds situmulins A (1) and B (2). The structures of 1 and 2 were established through the extensive analyses of 1D and 2D NMR spectral data together with the comparisons with the known compounds. Furthermore, the absolute configuration of 1 was determined by the time-dependent density functional theory (TDDFT) ECD approach, while the relative configuration of 2 was assigned via the quantum mechanical-NMR (QM-NMR) calculations. It might be worth to point out it is the first time to disclose the presence of cembrane diterpenes in the title species. In the bioassays, compound 2 not only showed strong antibacterial activities against fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with both minimum inhibitory concentration for 90 % (MIC90 ) values of 25 µM, but also demonstrated substantial inhibitory efficacy against vancomycin-resistant Enterococcus faecium bacteria G1, G4, G7, G8 and G13 from several individuals, with MIC90 values of 25, 50, 100, 50 and 25 µM, respectively.

Bta-miR-484 Targets SFRP1 and Affects Preadipocytes Proliferation, Differentiation, and Apoptosis.

MicroRNAs (miRNAs) are essential regulators of numerous biological processes in animals, including adipogenesis. Despite the abundance of miRNAs associated with adipogenesis, their exact mechanisms of action remain largely unknown. Our study highlights the role of bta-miR-484 as a major regulator of adipocyte proliferation, apoptosis, and differentiation. Here, we demonstrated that the expression of bta-miR-484 initially increased during adipogenesis before decreasing. Overexpression of bta-miR-484 in adipocytes ultimately inhibited cell proliferation and differentiation, reduced the number of EdU fluorescence-stained cells, increased the number of G1 phase cells, reduced the number of G2 and S phase cells, and downregulated the expression of proliferation markers (CDK2 and PCNA) and differentiation markers (CEBPA, FABP4, and LPL). Additionally, overexpression of bta-miR-484 promoted the expression of apoptosis-related genes (Caspase 3, Caspase 9, and BAX), and increased the number of apoptotic cells observed via flow cytometry. In contrast, bta-miR-484 inhibition in adipocytes yielded opposite effects to those observed during bta-miR-484 overexpression. Moreover, luciferase reporter assays confirmed SFRP1 as a target gene of bta-miR-484, and revealed that bta-miR-484 downregulates SFRP1 mRNA expression. These findings offer compelling evidence that bta-miR-484 targets SFRP1, inhibits proliferation and differentiation, and promotes apoptosis. Therefore, these results offer novel insights into the bta-miR-484 regulation of adipocyte growth and development.