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Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

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Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor‐induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2‐lacking, Ca2+‐permeable AMPA receptors (CP‐AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes. Strikingly, FK506 treatment reduced GluA1/GluA2 heteromers in both synaptosomes and endoplasmic reticulum‐enriched fractions from the PVN. Blocking CP‐AMPARs with IEM‐1460 induced a larger reduction of AMPAR‐mediated excitatory postsynaptic current (AMPAR‐EPSC) amplitudes in retrogradely labelled, spinally projecting PVN neurons in FK506‐treated rats than in vehicle‐treated rats. Furthermore, FK506 treatment shifted the current–voltage relationship of AMPAR‐EPSCs from linear to inward rectification in labelled PVN neurons. FK506 treatment profoundly enhanced physical interactions of α2δ‐1 with GluA1 and GluA2 in the PVN. Inhibiting α2δ‐1 with gabapentin, α2δ‐1 genetic knockout, or disrupting α2δ‐1–AMPAR interactions with an α2δ‐1 C terminus peptide restored GluA1/GluA2 heteromers in the PVN and diminished inward rectification of AMPAR‐EPSCs in labelled PVN neurons induced by FK506 treatment. Additionally, microinjection of IEM‐1460 or α2δ‐1 C terminus peptide into the PVN reduced renal sympathetic nerve discharges and arterial blood pressure elevated in FK506‐treated rats but not in vehicle‐treated rats. Thus, calcineurin in the hypothalamus constitutively regulates AMPAR subunit composition and phenotypes by controlling GluA1/GluA2 interactions with α2δ‐1. Synaptic CP‐AMPARs in PVN presympathetic neurons contribute to augmented sympathetic outflow in CIH. Key points: Systemic treatment with the calcineurin inhibitor increases serine phosphorylation of synaptic GluA1 and GluA2 in the PVN.Calcineurin inhibition enhances the prevalence of postsynaptic Ca2+‐permeable AMPARs in PVN presympathetic neurons.Calcineurin inhibition potentiates α2δ‐1 interactions with GluA1 and GluA2, disrupting intracellular assembly of GluA1/GluA2 heterotetramers in the PVN.Blocking Ca2+‐permeable AMPARs or α2δ‐1–AMPAR interactions in the PVN attenuates sympathetic outflow augmented by the calcineurin inhibitor. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to compare the effectiveness of interventions in cognitive function and frailty status and rank these interventions. Methods: Data Sources‐We searched PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, VIP and Google scholar. Data synthesis‐The risk of bias was assessed using the Cochrane risk bias assessment tool. Statistical heterogeneity was assessed using the Chi‐square test and quantified by I2. The results were pooled using the standardized mean difference (SMD). The rank probability for each intervention was calculated using the surface under the cumulative ranking curve (SUCRA). Additionally, the quality of the evidence was evaluated using the GRADE approach. Results: A total of 10 randomized controlled trials (RCTs) involving 1110 patients were included in our analysis. The network map of cognitive function comprised 9 RCTs with 1347 participants, examining eight different interventions. Nutritional support (SUCRA = 99.9%, SMD = 3.02, 95% CI: 2.53, 3.51) may be the most effective intervention to improve cognitive function. The network map of frailty (including 9 RCTs with 1017 participants and 9 interventions) suggested that multicomponent exercises (SUCRA = 96.4%, SMD = −5.10, 95% CI: −5.96, −4.23) tended to have a greater effect. Conclusions: Community‐based multicomponent exercises have shown significant benefits for improving cognitive function and frailty status in older adults, with moderate certainty. For hospitalized older patients with Cognitive frailty (CF), current evidence suggests that nutritional support yields the most improvement. Additionally, aerobic exercise and dual‐task training have proven effective in managing CF. Further studies are needed to validate these preliminary findings and exploring more accessible and effective physical and cognitive interventions to prevent CF in aging. Key points: The optimal interventions for frailty and cognition were multicomponent exercises and nutritional support.Doing multicomponent exercises in the community is likely the best effect on older adults with CF.Nutritional support may be the best improvement for hospitalized older adults with CF.Simultaneous cognitive/mindfulness training and physical exercises are effective components of CF management. [ABSTRACT FROM AUTHOR]

Hydrogen sulphide (H2S) is a gaseous neurotransmitter that can be self‐synthesized by living organisms. With the deepening of research, the pathophysiological mechanisms of endogenous H2S in cancer have been increasingly elucidated: (1) promote angiogenesis, (2) stimulate cell bioenergetics, (3) promote migration and proliferation thereby invasion, (4) inhibit apoptosis and (5) activate abnormal cell cycle. However, the increasing H2S levels via exogenous sources show the opposite trend. This phenomenon can be explained by the bell‐shaped pharmacological model of H2S, that is, the production of endogenous (low concentration) H2S promotes tumour growth while the exogenous (high concentration) H2S inhibits tumour growth. Here, we review the impact of endogenous H2S synthesis and metabolism on tumour progression, summarize the mechanism of action of H2S in tumour growth, and discuss the possibility of H2S as a potential target for tumour treatment. [ABSTRACT FROM AUTHOR]

Introduction Metabolic syndrome occurs in 20% of the population worldwide (Brown et al. 2001; Liu et al. 2010; Hanci et al. 2011; Angeloni et al. 2012). The main pathological characteristics [...], This study investigated the anti-arrhythmic effects from chronic intermittent hypobaric hypoxia (CIHH) and the cellular mechanisms in rats with metabolic syndrome. Male Sprague-Dawley rats were randomly distributed among the control, fructose-fed (fed with 10% fructose in the drinking water to induce metabolic syndrome), CIHH (42 days of hypobaric hypoxia treatment simulating an altitude of 5000 m a.s.l.: PB = 404 mm Hg, [PO.sub.2] = 84 mm Hg, 6 h per day), and the CIHH plus fructose (CIHH-F) groups. In anesthetized rats, the arrhythmia score was determined after 30 min of cardiac ischemia followed by 120 min of reperfusion. Action potentials (AP) were recorded from isolated ventricular papillary muscles. The arrhythmia score was much lower in CIHH-F rats than in the fructose-fed rats. Under basic conditions, AP duration (APD) was significantly shortened in fructose-fed rats, but obviously prolonged in CIHH rats compared with that of the control rats. During ischemia, the AP amplitude, the maximal rate of rise of phase 0, APD, and resting potential, were lower in the control, fructose-fed, and CIHH-F groups, but were not changed in the CIHH rats. The lower AP during ischemia did not recover after washout for the fructose-fed rats. In conclusion, CIHH protects the heart against ischemia-reperfusion induced arrhythmia in rats with metabolic syndrome. This effect of CIHH is possibly related to baseline prolongation of the AP and attenuation of AP reduction during ischemia-reperfusion. Key words: chronic intermittent hypobaric hypoxia, metabolic syndrome, ischemia-reperfusion, papillary muscle, action potential. Cette etude s'est penchee sur l'effet anti-arythmique d'une hypoxie hypobare intermittente chronique (HHIC) et ses mecanismes cellulaires chez des rats atteints du syndrome metabolique. Des rats males Sprague-Dawley ont ete repartis de maniere aleatoire en groupes controle, nourri au fructose (Fruc, nourri avec 10 % de fructose dans l'eau de consommation afin d'induire le syndrome metabolique), HHIC (42 jours d'hypoxie hypobare simulant une altitude de 5000 m : PB 404 mm Hg, [PO.sub.2] = 84 mm Hg, 6 heures par jour), et HHIC et fructose (HHIC-F). L'indice d'arythmie a ete determine chez les rats anesthesies apres 30 min d'ischemie cardiaque suivie d'une reperfusion de 120 min. Les potentiels d'action (PA) ont ete enregistres a partir des muscles ventriculaires papillaires isoles. L'indice d'arythmie etait beaucoup plus faible chez les rats du groupe HHIC-F que ceux du groupe Fruc. En condition de base, la duree du PA (DPA) etait significativement raccourcie chez les rats du groupe Fruc, mais prolongee de maniere evidente chez les rats HHIC comparativement a ceux du groupe controle. Durant l'ischemie, l'amplitude du PA, le taux maximal d'elevation de la phase 0, le DPA et le potentiel au repos etaient plus faibles chez les groupes controle, Fruc et HHIC-F, mais ils etaient inchanges chez les rats du groupe HHIC. Le PA plus faible durant l'ischemie n'etait pas retabli apres un rincage chez les rats Fruc. En conclusion, l'HHIC protege le coeur de l'arythmie induite par ischemie/reperfusion chez les rats atteints du syndrome metabolique. Cet effet de l'HHIC est possiblement relie a la prolongation de la ligne de base du PA et a l'attenuation de la reduction du PA durant l'ischemie-reperfusion. [Traduit par la Redaction] Mots-cles : hypoxie hypobare intermittente chronique, syndrome metabolique, ischemie-reperfusion, muscle papillaire, potentiel d'action.

Introduction In recent years the endocannabinoid system has emerged as a new therapeutic target in a variety of disorders associated with inflammation and tissue injury, including those of the cardiovascular [...], The aim of this study was to investigate whether the mitochondrial permeability transition pore (MPTP) opening was involved in the protective effects of CB2 receptor against ischemia-reperfusion (I-R) injury. For this, isolated perfused rat hearts were subjected to 30 min global ischemia followed by 120 min reperfusion, and left ventricle function was recorded. At the end of reperfusion, the infarct size in the hearts was measured by staining with triphenyltetrazolium chloride. MPTP opening and the mitochondrial membrane potential (Δ[Ψ.sub.m]) were measured by flow cytometry. Western blot analysis of cytochrome c in the mitochondrion and cytosol, as well as ERK1/2 and p-ERK1/2 were performed. Administration of CB2 receptor agonist JWH133 before ischemia significantly improved the recovery of cardiac ventricular function during reperfusion, increased coronary flow, reduced infarct size, prevented the loss of Δ[Ψ.sub.m] and MPTP opening, reduced the release of cytochrome c from mitochondria, and increased levels of p-ERK1/2. These effects of JWH133 were abolished by pretreatment with CB2 receptor antagonist AM630, or ERK1/2 inhibitor PD98059. Furthermore, JWH133 reversed the MPTP opening induced by atractyloside. The protective effect of JWH133 on the heart against I-R injury may be through increased ERK1/2 phosphorylation, inhibiting MPTP opening. Key words: JWH133, CB2 receptor, ischemia-reperfusion, mitochondrial permeability transition pore, ERK1/2, cardioprotection, rat. Afin de determiner si l'ouverture du pore de transition de permeabilite mitochondrial (PTPM) etait implique dans les effets protecteurs du recepteur CB2 envers le dommage d'ischemie-reperfusion (I-R), des cceurs de rats isoles ont ete soumis a une ischemie globale de 30 minutes suivie d'une reperfusion de 120 min, et la fonction ventriculaire gauche a ete enregistree. A la fin de la reperfusion, la taille de l'infarctus cardiaque a ete mesuree par une coloration au chlorure de triphenyltetrazolium, et l'ouverture du PTP et le potentiel membranaire mitochondrial (Δ[Ψ.sub.m]) ont ete mesures par cytometrie de flux. Des analyses par buvardage Western du cytochrome c mitochondrial et cytosolique, de ERK1/2 et de pERK1/2 ont ete realisees. L'administration de JWH133, un agoniste du recepteur CB2, prealablement a l'ischemie ameliorait significativement la recuperation de la fonction cardiaque ventriculaire lors de la reperfusion, augmentait le flux coronaire, reduisait la taille de l'infarctus, prevenait la perte de Δ[Ψ.sub.m] et l'ouverture du PTPM, reduisait la liberation de cytochrome c mitochondrial et augmentait la quantite de pERK1/2. Ces effets du JWH133 etaient abolis par un traitement prealable avec un antagoniste du recepteur CB2, le AM630, ou un inhibiteur de ERK1/2, le PD98059. De plus, le JWH133 pouvait renverser l'ouverture du PTPM induite par l'atractyloside, un agent qui ouvre le PTPM. L'effet protecteur du JWH133 sur le ccur envers le dommage d'I-R pourrait dependre d'une augmentation de la phosphorylation de ERK1/2 afin d'inhiber l'ouverture du PTPM. [Traduit par la Redaction] Mots-cles: WH133, recepteur CB2, ischemie-reperfusion, pore de transition de permeabilite mitochondrial, ERK1/2, cardioprotection, rat.

Comprehensive Summary: In this study, 27 new sesquiterpenoids: twenty monomers and seven dimers, with diverse structures, along with one known chlorajaponilide F (25) were isolated from the aerial parts of Chloranthus henryi var. hupehensis. Structurally, chlorahupetolides A (1) and B (2), two eudesmane‐type merosesquiterpenoids with an undescribed C18 carbon framework, and chlorahupetene E (18) are the first example of dimers comprising two eudesmane sesquiterpenoids bridged by a four‐membered ring in the Chloranthus. Their structures were characterized by nuclear magnetic resonance (NMR), electronic circular dichroism (ECD), and X‐ray diffraction analysis. In the RAW264.7 macrophages model of inflammation induced by LPS, compounds 12, 18, and 25 significantly reduced NO production in a dose dependent manner and without cytotoxicity. The mRNA expression of COX‐2 was considerably inhibited by treatments with compounds 12, 18, and 25. [ABSTRACT FROM AUTHOR]

Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex (FAC) which is composed of FLOWERING LOCUS T (FT), FD, and 14‐3‐3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing (AS) of CiFD, forming two different proteins (CiFDα and CiFDβ). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence (CiFD‐DNA), CiFDα, or CiFDβ in tobacco and citrus showed early flowering, and CiFD‐DNA transgenic plants were the earliest, followed by CiFDβ and CiFDα. Interestingly, CiFDα and CiFDβ were induced by low temperature and drought, respectively. Further analysis showed that CiFDα can form a FAC complex with CiFT, Ci14‐3‐3, and then bind to the citrus APETALA1 (CiAP1) promoter and promote its expression. However, CiFDβ can directly bind to the CiAP1 promoter independently of CiFT and Ci14‐3‐3. These results showed that CiFDβ can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought‐induced flowering through AS. In addition, a bHLH transcription factor (CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought‐ and low‐temperature‐induced citrus flowering through different regulatory patterns. [ABSTRACT FROM AUTHOR]

Flower induction in adult citrus is mainly regulated by drought and low temperatures. However, the mechanism of FLOWERING LOCUS T regulation of citrus flowering (CiFT) under two flower‐inductive stimuli remains largely unclear. In this study, a citrus transcription factor, nuclear factor YA (CiNF‐YA1), was found to specifically bind to the CiFT promoter by forming a complex with CiNF‐YB2 and CiNF‐YC2 to activate CiFT expression. CiNF‐YA1 was induced in juvenile citrus by low temperature and drought treatments. Overexpression of CiNF‐YA1 increased drought susceptibility in transgenic citrus, whereas suppression of CiNF‐YA1 enhanced drought tolerance in silenced citrus plants. Furthermore, a GOLDEN2−LIKE protein (CiFE) that interacts with CiFT protein was also isolated. Further experimental evidence showed that CiFE binds to the citrus LEAFY (CiLFY) promoter and activates its expression. In addition, the expressions of CiNF‐YA1 and CiFE showed a seasonal increase during the floral induction period and were induced by artificial drought and low‐temperature treatments at which floral induction occurred. These results indicate that CiNF‐YA1 may activate CiFT expression in response to drought and low temperatures by binding to the CiFT promoter. CiFT then forms a complex with CiFE to activate CiLFY, thereby promoting the flowering of adult citrus. Summary statement: FLOWERING LOCUS T (FT) plays a central role in citrus flowering. This study demonstrated that citrus NF‐YA1 may activate FT expression in response to drought and low temperature by interacting with FE, and that the FT‐FE complex activates LEAFY, thereby promoting the flowering of adult citrus. [ABSTRACT FROM AUTHOR]