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Wen-Chun Chen,1– 3 Chiu-Chu Lin,2,4,5 Chia-Chi Kuo,6,7 Chia-Chen Wu,8 Tz-Jie Liu,9 Mei-Tsu Chen9 1Department of Community Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan; 2School of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Nursing, Chang Jung University of Science and Technology, Chiayi Campus, Tainan, Taiwan; 4Department of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Emergency Department, Chi-Mei Medical Center, Tainan, Taiwan; 7Department of Nursing, Chang Jung Christian University, Tainan, Taiwan; 8School of Nursing, Fooyin University, Kaohsiung, Taiwan; 9Health Management Center, St. Martin De Porres Hospital, Chiayi, TaiwanCorrespondence: Chiu-Chu Lin Email chiuchu@kmu.edu.twObjective: To improve the quality of peer leader training, this study developed a theory-based self-management training program for older adult peer leaders with diabetes and assessed its feasibility.Background: Current self-management programs are designed mainly to be implemented by healthcare professionals, but healthcare staff may not fully perceive the needs and obstacles of older adults in disease management due to a lack of similar illness experience. To target this problem, peer leaders with successful self-management experiences, similar cultural backgrounds and languages, and related illness experiences are trained to guide and mentor peer patients in self-management programs.Study Design and Methods: This study was conducted in two stages. In stage 1, a peer leader training program was developed based on experiential learning theory as the framework and self-regulation theory as the activity design strategy. In stage 2, program feasibility was assessed via participants’ feedback toward the training program by three indicators: attendance, future willingness to lead the peer-led self-management program, and leadership skills evaluated by a peer leader training assessment tool.Results: In this study, peer leaders demonstrated good leadership skills by expressing active willingness to lead self-management programs in the community. Peer leaders’ feedback indicated that the program’s training content was helpful in preparing peer leaders to guide older adults in learning self-management skills and in improving the abilities and confidence of peer leaders in mentoring self-management.Conclusion: Findings in this study showed that peer leader training can impact the effectiveness and success of self-management in older adults with diabetes. Even in a small-scale study, the impact was evident, which demonstrated the feasibility of the program. More large-scale studies on the effectiveness of various peer leader training programs in diverse disciplines are recommended.Clinical Trials Registry: ClinicalTrials.gov Identifier: NCT04298424 (the Peer-Led Self-Management Program).Keywords: older adult, peer leader, diabetes, theory-based, peer-led, self-management

Estimates of the change in surface seawater δ18O (δ18Osw) between the Last Glacial Maximum (LGM) and Late Holocene (LH) are derived from homogenous data sets with rigorous age control, namely MARGO sea surface temperature (SST) estimates and oxygen isotopic ratios (δ18O) of planktonic foraminifers. Propagation of uncertainties associated with each proxy allows the identification of robust patterns of change in δ18Osw. Examination of these patterns on a regional scale highlights which changes in surface currents and hydrological cycle are consistent with both planktonic isotopic data and reconstructed SST. Positive local annual mean LGM-LH δ18Osw anomalies characterize the glacial tropical Indian Ocean, portions of the western and eastern margins of the North Pacific, the Iberian margin and the tropical North Atlantic, as well as the South African margin. Although reduced precipitation during the LGM with respect to the LH may have contributed to some extent to these local enrichments in surface seawater 18O, the largest positive anomalies appear to be related to changes in ocean circulation. Large local negative annual mean LGM-LH δ18Osw anomalies are found in the South Pacific and North Atlantic, reflecting the equatorward migration of surface temperature fronts during the LGM with respect to the LH. In the northern North Atlantic, a region characterized by large discrepancies between SST estimates based on different proxies, only SST estimates based on planktonic foraminifer counts yield annual mean LGM-LH δ18Osw anomalies consistent with a southward shift of the polar front at the LGM relative to the LH.

Contents [ABSTRACT FROM AUTHOR]

This study investigates the potential of antimicrobial peptides (AMPs) as alternatives to combat antibiotic resistance, with a focus on two AMPs containing unnatural amino acids (UAAs), E2-53R (16 AAs) and LE-54R (14 AAs). In both peptides, valine is replaced by norvaline (Nva), and tryptophan is replaced by 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). Microbiological studies reveal their potent activity against both Gram-negative (G(-)) and Gram-positive (G(+)) bacteria without any toxicity to eukaryotic cells at test concentrations up to 32 μM. Circular dichroism (CD) spectroscopy indicates that these peptides maintain α-helical structures when interacting with G(-) and G(+) lipid model membranes (LMMs), a feature linked to their efficacy. X-ray diffuse scattering (XDS) demonstrates a softening of G(-), G(+) and eukaryotic (Euk33) LMMs and a nonmonotonic decrease in chain order as a potential determinant for bacterial membrane destabilization. Additionally, XDS finds a significant link between both peptides' interfacial location in G(-) and G(+) LMMs and their efficacy. Neutron reflectometry (NR) confirms the AMP locations determined using XDS. Lack of toxicity in eukaryotic cells may be related to their loss of α-helicity and their hydrocarbon location in Euk33 LMMs. Both AMPs with UAAs offer a novel strategy to wipe out antibiotic-resistant strains while maintaining human cells. These findings are compared with previously published data on E2-35, which consists of the natural amino acids arginine, tryptophan, and valine.

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults., Methods: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for., Results: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (β =  - 0.036 and β = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (β =  - 0.008 and β = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (β =  - 0.026 and β =  - 0.053, respectively, P < 0.05)., Conclusions: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations., (© 2024. The Author(s).)

Importance: Hypertension is increasingly common in pregnancy capable individuals, yet there is limited data on antihypertensive medication dispensation in peripartum individuals., Objective: To describe antihypertensive medication dispensation from preconception through the first year postpartum., Design, Setting, and Participants: This retrospective cohort study used the Truven Health Market Scan administrative data from 2008 to 2014 to identify women in the United States with commercial or government health insurance, aged 15-54, free from heart disease, who experienced a pregnancy and filled at least 1 prescription for an antihypertensive medication between 3 months prior to conception and 12 months after the end of the pregnancy., Main Outcomes and Measures: We describe antihypertensive dispensation patterns (continuation, initiation, and discontinuation) by medication class during 5 time periods: preconception, first, second, and third trimesters, and the first year postpartum., Results: Of 1,058,521 pregnancies, 108,614 (10.3%) were exposed to at least 1 antihypertensive medication dispensation. The most commonly dispensed medications across all periods combined were adrenergic blockers, calcium channel blockers (CCBs), and diuretics. Renin-angiotensin-aldosterone system (RAAS) inhibitors were the third most dispensed medication class in the preconception period (26.4%), and fills decreased to 5.7% and 1.7% in the second and third trimesters, respectively. Of the women with chronic hypertension who filled at least 1 prescription prior to conception, 8.4% were not dispensed an antihypertensive medication during the first year after delivery., Conclusions and Relevance: Antihypertensive prescription dispensation of both preferred and potentially harmful agents is common in pregnancy capable individuals. Patterns of dispensation suggest room for improvement in the treatment of chronic hypertension after a pregnancy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Open hollow dodecahedral cage clusters have long been a coveted target in synthetic chemistry, yet their creation poses immense challenges. Here we report two open hollow dodecahedral lanthanide-aluminum (Ln-Al) heterometallic cage clusters, namely, [Ln 210 Al 140 (μ 2 -OH) 210 (μ 3 -OH) 540 (OAc) 180 (H 2 O) 156 ](ClO 4 ) 120 ·(MeCN) x ·(H 2 O) y , (Ln = Dy and x = 27, y = 300 for 1 ; Ln = Y and x = 28, y = 420 for 2 ). Remarkably, the 350 metal atoms in 1 and 2 display a Keplerate-type four-shell structure of truncated icosidodecahedron@dodecahedron@dodecahedron@icosidodecahedron. The diameter of the cationic cluster in 1 is approximately 5.0 nm, with an inner cavity diameter of about 2.8 nm and a window diameter of roughly 0.66 nm. The cluster in 1 boasts an accessible inner void volume of up to 15,000 Å 3 . Notably, these cage clusters maintain stability in water, and the truncated icosidodecahedrons in 1 and 2 are the first of their kind synthesized to date. Given that the open hollow dodecahedral Ln-Al cage cluster has never been reported before, this work represents a member in the family of hollow open dodecahedral cages.

Adiabatic demagnetization refrigeration (ADR) is a promising cooling technology with high efficiency and exceptional stability in achieving ultralow temperatures, playing an indispensable role at the forefront of fundamental and applied science. However, a significant challenge for ADR is that existing magnetic refrigerants struggle to concurrently achieve low magnetic ordering temperatures ( T 0 ) and substantial magnetic entropy changes (-Δ S m ) at ultralow temperatures. In this work, we propose the combination of Gd 3+ and Yb 3+ to effectively regulate both -Δ S m and T 0 in ultralow temperatures. Notably, the -Δ S m values for Gd 0.1 Yb 0.9 F 3 ( 1 ) and Gd 0.3 Yb 0.7 F 3 ( 2 ) in the 0.4-1.0 K range exceed those of all previously reported magnetic refrigerants within this temperature interval, positioning them as the most efficient magnetic refrigerants for the third stage to date. Although the -Δ S m values for Gd 0.5 Yb 0.5 F 3 ( 3 ) in 1-4 K are less than those of the leading magnetic refrigerant Gd(OH)F 2 , the -Δ S m values for Gd 0.7 Yb 0.3 F 3 ( 4 ) in 1-4 K at 2 T surpass those of all magnetic refrigerants previously documented within the same temperature range, making it the superior magnetic refrigerant for the fourth stage identified thus far.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied., Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed., Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [ P = .03%] and 1.0% vs 3.8% [ P = .05], respectively)., Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Keggin-Fe 13 clusters are considered foundational building blocks or prenucleation precursors of ferrihydrite. Understanding the factors that influence the rotational configuration of these clusters, and their transformations in water, is vital for comprehending the formation mechanism of ferrihydrite. Here, we report syntheses and crystal structures of four lanthanide-iron-oxo clusters, namely, [Dy 6 Fe 13 (Gly) 12 (μ 2 -OH) 6 (μ 3 -OH) 18 (μ 4 -O) 4 (H 2 O) 17 ]·13ClO 4 ·19H 2 O ( 1 ), [Dy 6 Fe 13 (Gly) 12 (μ 3 -OH) 24 (μ 4 -O) 4 (H 2 O) 18 ]·13ClO 4 ·14H 2 O ( 2 ), [Pr 8 Fe 34 (Gly) 24 (μ 3 -OH) 28 (μ 3 -O) 30 (μ 4 -O) 4 (H 2 O) 30 ]·6ClO 4 ·20H 2 O ( 3 ), and [Pr 6 Fe 13 (Gly) 12 (μ 3 -OH) 24 (μ 4 -O) 4 (H 2 O) 18 ]·13ClO 4 ·22H 2 O ( 4 , Gly = glycine). Single-crystal analyses reveal that 1 has a β-Keggin-Fe 13 cluster, marking the first documented instance of such a cluster to date. Conversely, both 2 and 4 contain an α-Keggin-Fe 13 cluster, while 3 is characterized by four hexavacant ε-Keggin-Fe 13 clusters. Magnetic property investigations of 1 and 2 show that 2 exhibits ferromagnetic interactions, while 1 exhibits antiferromagnetic interactions. An exploration of the synthetic conditions for 1 and 2 indicates that a higher pH promotes the formation of α-Keggin-Fe 13 clusters, while a lower pH favors β-Keggin-Fe 13 clusters. A detailed analysis of the transition from 3 to 4 emphasizes that lacunary Keggin-Fe 13 clusters can morph into Keggin-Fe 13 clusters with a decrease in pH, accompanied by a significant change in their rotational configuration.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1β, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Carotenoids are natural lipophilic pigments, which have been proven to provide significant health benefits to humans, relying on their capacity to efficiently scavenge singlet oxygen and peroxyl radicals as antioxidants. Strains belonging to the genus Rhodosporidium represent a heterogeneous group known for a number of phenotypic traits including accumulation of carotenoids and lipids and tolerance to heavy metals and oxidative stress. As a representative of these yeasts, Rhodosporidium toruloides naturally produces carotenoids with high antioxidant activity and grows on a wide variety of carbon sources. As a result, R. toruloides is a promising host for the efficient production of more value-added lipophilic compound carotenoids, e.g., torulene and torularhodin. This review provides a comprehensive summary of the research progress on carotenoid biosynthesis in R. toruloides, focusing on the understanding of biosynthetic pathways and the regulation of key enzymes and genes involved in the process. Moreover, the relationship between the accumulation of carotenoids and lipid biosynthesis, as well as the stress from diverse abiotic factors, has also been discussed for the first time. Finally, several feasible strategies have been proposed to promote carotenoid production by R. toruloides. It is possible that R. toruloides may become a critical strain in the production of carotenoids or high-value terpenoids by genetic technologies and optimal fermentation processes. KEY POINTS: • Biosynthetic pathway and its regulation of carotenoids in Rhodosporidium toruloides were concluded • Stimulation of abiotic factors for carotenoid biosynthesis in R. toruloides was summarized • Feasible strategies for increasing carotenoid production by R. toruloides were proposed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022., Method: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively., Results: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels., Conclusions: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research., Competing Interests: Declaration of competing interest All authors of this manuscript have directly participated inplanning, execution, and/or analysis of this study. The contents of this manuscript have not been copyrighted or published previously. The contents of this manuscript are not now under consideration for publication elsewhere. The contents of this manuscript will not be copyrighted, submitted, or published elsewhere. There are no directly related manuscripts or abstracts, published or unpublished, by any authors of this manuscript. No financial support or incentive has been provided for this manuscript. I am one author signing on behalf of all co-authors of this manuscript, and attesting to the above., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aβ) transgenic nematodes by lowering endogenous FA levels and reducing Aβ aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aβ toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adiabatic demagnetization refrigeration is known to be the only cryogenic refrigeration technology that can achieve ultralow temperatures (≪1 K) at gravity-free conditions. The key indexes to evaluate the performance of magnetic refrigerants are their magnetic entropy changes (-Δ S m ) and magnetic ordering temperature ( T 0 ). Although, based on the factors affecting the -Δ S m of magnetic refrigerants, one has been able to judge if a magnetic refrigerant has a large -Δ S m , how to accurately predict their T 0 remains a huge challenge due to the fact that the T 0 of magnetic refrigerants is related to not only magnetic exchange but also single-ion anisotropy and magnetic dipole interaction. Here, we, taking GdCO 3 F ( 1 ), Gd(HCOO)F 2 , Gd 2 (SO 4 ) 3 ·8H 2 O, GdF 3 , Gd(HCOO) 3 and Gd(OH) 3 as examples, demonstrate that the T 0 of magnetic refrigerants with very weak magnetic interactions and small anisotropy can be accurately predicted by integrating mean-field approximation with quantum Monte Carlo simulations, providing an effective method for predicting the T 0 of ultralow-temperature magnetic refrigerants. Thus, the present work lays a solid foundation for the rational design and preparation of ultralow-temperature magnetic refrigerants in the future.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO 2max ), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion ( p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage ( p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 ( p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

Background: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo., Methods: The cytotoxic effect of DeHE on PDAC cells was assessed using CCK-8 and colony formation assays. The antitumor efficacy of DeHE were appraised in human PANC-1 xenograft mouse model. Sphere formation assay and flow cytometry were employed to quantify the tumor stemness. RNA-Seq analysis, drug affinity responsive target stability assay (DARTS), and RNA interference transfection were conducted to elucidate potential signaling pathways. Western blotting and immunohistochemistry were utilized to assess protein expression levels., Results: DeHE effectively inhibited PDAC cell proliferation and tumor growth in vitro and in vivo, and exhibited a better safety profile compared to the clinical drug gemcitabine (GEM). DeHE inhibited PCSCs, as evidenced by its suppression of self-renewal capabilities of PCSCs, reduced the proportion of ALDH + cells and downregulated stemness-associated proteins (Nanog, Sox-2, and Oct-4) both in vitro and in vivo. Furthermore, there is potential involvement of DDIT3 and its downstream DDIT3/TRIB3/AKT/mTOR pathway in the suppression of stemness characteristics within DeHE-treated PDAC cells. Additionally, results from the DARTS assay indicated that DeHE interacts with DDIT3, safeguarding it against degradation mediated by pronase. Notably, the inhibitory capabilities of DeHE on PDAC cell proliferation and tumor stemness were partially restored by siDDIT3 or the AKT activator SC-79., Conclusion: In summary, our study has identified DeHE, a novel antitumor natural product, as an activator of DDIT3 with the ability to suppress the AKT/mTOR pathway. This pathway is intricately linked to tumor cell proliferation and stemness characteristics in PDAC. These findings suggest that DeHE holds potential as a promising candidate for the development of innovative anticancer therapeutics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients., Materials and Methods: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups., Results: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level., Conclusion: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB)., Methods: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores., Results: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality., Conclusion: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB., (© 2024. The Author(s).)

A series of chiral heterometallic Ln-Co clusters, denoted as Co 2 Ln and Co 3 Ln 2 (Ln = Dy and Er), were synthesized by reacting the chiral chelating ligand ( R / S )-2-(1-hydroxyethyl)pyridine (Hmpm), CoAc 2 ·4H 2 O, and Ln(NO 3 ) 3 ·6H 2 O. Co 2 Ln and Co 3 Ln 2 exhibit perfect mirror images in circular dichroism within the 320-700 nm range. Notably, the Co 2 Er and Co 3 Er 2 clusters display pronounced magnetic circular dichroism (MCD) responses of the hypersensitive f-f transitions 4 I 15/2 - 4 G 11/2 at 375 nm and 4 I 15/2 - 2 H 11/2 at 520 nm of Er III ions. This study highlights the strong magneto-optical activity associated with hypersensitive f-f transitions in chiral 3d-4f magnetic clusters.

Objectives: This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA)., Methods: A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated., Results: The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013)., Conclusions: Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Seven asymmetric zinc benzamidinate complexes featuring or lacking side-arm functionalities were synthesized. Using equimolar zinc reagent produced distinct dinuclear motifs [(C 6 H 5 -C = NC 6 H 5 )ZnEt] 2 (R = t Bu, 1; (CH 2 ) 2 OMe, 2; (CH 2 ) 2 NMe 2 , 3). Half the zinc reagent yielded dinuclear [(C 6 H 5 -C = NC 6 H 5 ) 2 Zn] 2 (R = t Bu, 4) or mononuclear zinc bis(chelate) complexes (R = (CH 2 ) 2 OMe, 5; (CH 2 ) 2 NMe 2 , 6; CH 2 Py, 7). Molecular structures of 1-4 and 7 were determined via single-crystal X-ray diffraction. Altering benzamidinate substituents modifies both coordination modes and catalytic activities in ring-opening polymerization of L-lactide. Specifically, complex 7 exhibits enhanced catalytic activity at 25 °C using 100 equivalents of L-lactide with a turnover frequency of 1820 h -1 .

Welded steel plates are widely used in various structural applications, and the presence of inclined welds is often encountered in practical scenarios. Carbon fiber reinforced polymer (CFRP) has been proven to be effective for strengthening steel structures. However, the behavior of CFRP-strengthened welded steel plates with inclined welds, particularly considering the influence of welding residual stress, is limited. This paper aims to investigate the tensile behavior of CFRP-strengthened welded Q355 steel plates with inclined welds considering welding residual stress (WRS). First, WRS data were obtained by the X-ray diffraction (XRD) method at different locations. The maximum tensile and compressive residual stresses are 0.39 and 0.14 times the yield strength of the steel, respectively. Then, finite element models were established to investigate the effects of weld angles, weld width, and height on the WRS distribution of welded steel plates. Finally, the tensile performance of CFRP-strengthened welded plates with WRS was studied by numerical simulation. The results showed that the weld angles have little effect on the distribution pattern of residual stress but significantly affect the peak tensile WRS. When the weld angle changes from 0° to 60°, the peak tensile WRS decreases significantly from 0.32 to 0.06 times the yield strength of steel; furthermore, the influence of weld width and height on WRS is relatively limited. Under tension loading, the maximum stress occurs near the weld. The ends of the weld enter the yielding state later than the middle part of the weld due to the distribution of the WRS. As the weld angle increases and the length of the weld increases, the stress in the weld zone decreases, while the stress in the base material zone correspondingly increases. In addition, CFRP strengthening can reduce the magnitude of stress. This study provides preliminary references for understanding the tensile behavior of CFRP-strengthened welded steel plates with inclined welds.

Objective: To systematically screen and identify long noncoding RNA (lncRNA) associated with bone marrow adiposity changes in aplastic anemia (AA)., Methods: The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened. The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC, BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls., Results: PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC, and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC. PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner. The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls., Conclusion: PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC, and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.

Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson's disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans ; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Han, Wu, Zhou, Chen, Zhang, Ma and Feng.)

Five decanuclear lanthanide-iron clusters, formulated as [Ln 2 Fe 8 (hmp) 10 (μ 2 -OH) 4 (μ 3 -OH) 2 (μ 4 -O) 4 (H 2 O) 6 ]·6ClO 4 · x H 2 O ( x ≈ 8, Ln = Y for 1; x ≈ 6, Ln = Dy for 2; x ≈ 6, Ln = Ho for 3; x ≈ 7, Ln = Tb for 4; x ≈ 7, Ln = Gd for 5, Hhmp = 2-(hydroxymethyl)pyridine), have been synthesized and structurally characterized. Single-crystal structural analysis reveals that the cluster consists of six face-sharing defective cubane units. Dynamic magnetic investigations indicated that cluster 2 exhibits single-molecule magnet behavior under a zero dc field eliciting an effective energy barrier of U eff = 17.76 K and a pre-exponential factor of τ 0 = 7.93 × 10 -8 s. Investigation of the performance of a series of Fe III -Dy III SMMs indicates that the relatively low energy barrier in 2 is associated with the weak ferromagnetic coupling between Fe III and Dy III ions, while the strength of ferromagnetic interaction in these clusters is mainly related to the bond distances between Dy III and O atoms coordinated to Fe III ions. Clusters 3 and 4 exhibit similar dual relaxation pathways under their respective optimal external applied dc field, where the direct relaxation process occurs in the low-frequency area, which impedes the extraction of the U eff , while the secondary relaxation process appears at a higher frequency, which is probably a connection with intermolecularly driven relaxation. Our findings offer a magneto-structural correlation model for further investigating the single-molecule magnet behavior in lanthanide-iron systems.

Context: The highly infectious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused large-scale transmission from Dec 2022 to Feb 2023 in China. After this event, a remarkable surge of influenza A (Flu A) occurred from March to May 2023, especially in pediatric patients., Objectives: This study aimed to investigate the differences between pediatric patients infected with COVID-19 Omicron and Flu A virus., Methods: A total of 1,063 hospitalized children who admitted into two tertiary general hospital of Guangdong province of China were included. Medical records were compared retrospectively in these patients during the pandemic periods of SARS-CoV-2 omicron and Flu A., Results: A total of 592 Patients with Flu A were mostly preschool and school-aged (>3y, 76.0%), they showed higher ratio of high fever (≥39°C), cough, rhinorrhea, and vomiting than patients with SARS-CoV-2 omicron. Most of the 471 Omicron patients were young children (0-3y, 74.5%) and had more poor appetite and dyspnea symptom. Benign acute children myositis (BACM) was only observed in patients with Flu A, and a significant male predominance. Multisystem inflammatory syndrome in children (MIS-C) was only found in patients with SARS-CoV-2 Omicron. Compared to the SARS-CoV-2 Omicron group, for both age groups (0-3 years and > 3 years), the Flu A group showed significantly reduced lymphocyte (Lym) counts ( P < 0.001), and elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CK-MB) in laboratory indexes (all P < 0.001). Additionally, it was found that more children hospitalized with COVID-19 had increased C-reactive protein (CRP) levels compared to those with Flu A., Conclusion: Influenza A infections have notably surged in children, coinciding with the relaxation of COVID-19 related social restrictions. During the epidemic periods of Omicron and Flu A virus infection, different clinical and laboratory characteristics were observed in hospitalized children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Chen, Zhang, Wu, Xie, Guan, Yang, Cai, Wen and Yang.)

Bleeding from a visceral artery pseudoaneurysm (VAPA) is a rare but significant complication of bariatric surgery. Patients may present with gastrointestinal (GI) haemorrhage in the forms of haematemesis, melaena, haematochezia or haemodynamic compromise. Although CT angiogram, endoscopy and laparoscopy form essential parts of diagnostic assessment, small pseudoaneurysms with intermittent bleeding may be overlooked. We report the case of a man in his 40s who presented to the emergency department with massive GI bleeding and subsequent haemodynamic instability, secondary to a pseudoaneurysm from a vascular injury during a recent bariatric procedure. This case highlights the diagnostic challenges of obscure, intermittent bleeding involving the bypassed stomach with unremarkable investigation findings, and aims to raise awareness among clinicians in considering the less common postgastric-bypass complications., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, various halogen-substituted Grignard reagents were assessed as deprotonating agents for the oxazoline-amido-phenolate ligand, leading to the formation of magnesium complexes. The newly synthesized complexes with halogen substituents displayed three distinct coordinative modes, all extensively characterized through crystallographic methods. The introduction of halogen substituents induced changes in the Lewis acid properties of the complexes, thereby impacting their structural attributes and catalytic behavior during the initiation and propagation of ring polymerization of cyclic esters.

Purpose: To evaluate the association between the change in the number of PIMs in older adults during hospitalization and adverse outcomes., Methods: This retrospective cohort study was conducted in the internal medicine wards of a tertiary teaching hospital between May and December 2017. 3,460 patients (77.5±8.4 years, 60.4% male) were enrolled, and 206 patients died during hospitalization. PIMs were defined using the Beers Criteria as suggested by the American Geriatrics Society. Adverse outcomes studied were functional decline (a loss in 1 or more activities of daily living from admission to discharge), prolonged length of stay (LOS) (≥14 days), and mortality., Results: 2258 patients (65.3%) had increasing PIMs during hospitalization. They tended to be younger (77.0±8.3 versus 78.5±8.5 years, p<0.001) and had lower numbers of PIMs at admission (0.4±0.8 versus 0.8±1.1, p<0.001). Increasing PIM use was strongly associated with greater functional decline (aOR 1.36, 95%CI 1.01-1.67, p=0.005), prolonged LOS (aOR 3.47, 95%CI 2.71-4.44, p<0.001) and higher mortality rate (aOR 2.68, 95%CI 1.75-4.12, p<0.001), even after adjusting for all covariates. We observed a strong association between adverse outcomes and increasing PIMs in older adults during hospitalization (p for trend <0.001)., Conclusions: Older adults with increasing PIMs during hospitalization were at greater risk for functional decline, prolonged LOS, and mortality, especially in those with three or more PIMs. Further studies are needed to better understand the complex interactions and to evaluate the effectiveness of intervention programs to lower PIM number and improve discharge outcomes for patients who had increasing PIM use during hospitalization., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases., Aim of the Study: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms., Materials and Methods: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E 2 (PGE 2 ) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein., Results: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE 2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein., Conclusion: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although novel agents for multiple myeloma (MM) have a better response rate and survival in both newly diagnosed and relapsed/refractory MM patients, concerns regarding the association between MM treatments and thromboembolic events have been raised. The aim of this population-based study was to examine the association between different combinations of MM treatments and the risk of thromboembolic events. We conducted a nested case-control study using the Taiwan Cancer Registry (TCR) and National Health Insurance Research Database (NHIRD). Adult patients newly diagnosed with MM and treated with at least one of the immunomodulatory agents between 2008 and 2016 were identified. Among them, we further identified patients who developed thromboembolic events as cases and selected controls matched by age, sex and duration of MM diagnosis at a ratio of 1:5. The index date was defined as the day one year before the diagnosis date of thromboembolic events in the case group and the corresponding date in the control group. Conditional logistic regression was used to examine the association between different MM treatment regimens and the risk of thromboembolic events. A total of 4,180 newly diagnosed MM patients treated with at least one of the immunomodulatory agents were identified (mean age: 67.2 years; male: 55.7%). In this MM cohort, we further identified 388 cases and 1,940 matched controls (mean age: 71 years; male: 64.2%). The use of a thalidomide/bortezomib/steroid combination (odds ratio (OR) 2.95 [95% confidence interval (CI) 1.47-5.95]), thalidomide monotherapy (OR 3.33; 95% CI, 1.59-6.94), and a thalidomide/steroid combination (OR 4.24; 95% CI, 2.00-8.98) were associated with an increased risk of thromboembolic events. Other risk factors, particularly a history of thromboembolic events, including ischemic heart disease and pulmonary embolism, were significantly associated with increased risk of thromboembolic events. We found that the use of thalidomide alone and in specific combinations was associated with an increased risk of thromboembolic events., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During the course of treating non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutant, gefitinib resistance (GR) is unavoidable. As the environment for tumor cells to grow and survive, tumor microenvironment (TME) can significantly affect therapeutic response and clinical outcomes, offering new opportunities for addressing GR. Dynamic changes within the TME were identified during the treatment of gefitinib, suggesting the close relationship between TME and GR. Various dynamic processes like angiogenesis, hypoxia-pathway activation, and immune evasion can be blocked so as to synergistically enhance the therapeutic effects of gefitinib or reverse GR. Besides, cellular components like macrophages can be reprogrammed for the same purpose. In this review, we summarized recently proposed therapeutic targets to provide an overview of the potential roles of TME in treating gefitinib-resistant NSCLC, and discussed the difficulty of applying these targets in cancer treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)