Characteristics of bone mineral density in patients with functional hypothalamic amenorrhoea and its association with reproductive hormones and body composition.

OBJECTIVE: Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. DESIGN: To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. PATIENTS: We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. MEASUREMENTS: The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 ) and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM) and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMD and femoral neck BMD in patients with FHA, and the Z score was calculated. RESULTS: The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (ß = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (ß = .046, 95% CI = 0.013-0.080, p = .008). CONCLUSION: Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.

Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells.

Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.

Pantranscriptome combined with phenotypic quantification reveals germplasm kinship and regulation network of bract color variation in Bougainvillea.

Bracts are the metamorphic non-flower organ in angiosperm plants. The variation of the color and shape of bracts was found to be neo-functionalized (i.e., similar to petals), garnering research interest as a pollinator attractor. Bougainvillea is known for its specialized, large, and colorful bracts, which contrast with its tiny colorless flowers. As a plant whose bracts vary greatly in terms of coloration, the molecular mechanisms for Bougainvillea bract coloration and polychroism are largely unknown. The lack of genomic information for Bougainvillea largely hinders studies into the evolution and genetic basis of bract color variation. In this study, a pan-transcriptome of bracts obtained from 18 Bougainvillea glabra accessions was employed to investigate the global population-level germplasm kinship and the gene regulation network for bract color variation. Our results showed that the bracts of B. glabra accessions have largely differentiated International Commission on Illumination (CIE) L-a-b values. Moreover, germplasm kinship detected using principal component analysis, phylogeny, and admixture analysis showed three optimal subgroups, two of them distinctly clustered, which were not directly correlated with bract color variation at the population level. Differentially expressed genes (DEGs) between accessions of high vs. low L-a-b values revealed several considerable upregulated genes related to bract color L-a-b variation. A weighted gene co-expression network was constructed, and eight co-expressed regulation modules were identified that were highly correlated with variation in bract CIE L-a-b color values. Several candidate DEGs and co-expressed hub genes (e.g., GERD, SGR, ABCA3, GST, CYP76AD1, CYP76C, and JAZ) that were tightly associated with bract color variation were eventually determined responsible for L-a-b colorations, which might be the core regulation factors contributing to the B. glabra bract color variation. This study provides valuable insights into the research on germplasm kinship, population-level pan-transcriptome expression profiles, and the molecular basis of color variation of key innovative bracts in horticultural Bougainvillea.

Genome-wide identification and adaptive evolution of CesA/Csl superfamily among species with different life forms in Orchidaceae.

Orchidaceae, with more than 25,000 species, is one of the largest flowering plant families that can successfully colonize wide ecological niches, such as land, trees, or rocks, and its members are divided into epiphytic, terrestrial, and saprophytic types according to their life forms. Cellulose synthase (CesA) and cellulose synthase-like (Csl) genes are key regulators in the synthesis of plant cell wall polysaccharides, which play an important role in the adaptation of orchids to resist abiotic stresses, such as drought and cold. In this study, nine whole-genome sequenced orchid species with three types of life forms were selected; the CesA/Csl gene family was identified; the evolutionary roles and expression patterns of CesA/Csl genes adapted to different life forms and abiotic stresses were investigated. The CesA/Csl genes of nine orchid species were divided into eight subfamilies: CesA and CslA/B/C/D/E/G/H, among which the CslD subfamily had the highest number of genes, followed by CesA, whereas CslB subfamily had the least number of genes. Expansion of the CesA/Csl gene family in orchids mainly occurred in the CslD and CslF subfamilies. Conserved domain analysis revealed that eight subfamilies were conserved with variations in orchids. In total, 17 pairs of CesA/Csl homologous genes underwent positive selection, of which 86%, 14%, and none belonged to the epiphytic, terrestrial, and saprophytic orchids, respectively. The inter-species collinearity analysis showed that the CslD genes expanded in epiphytic orchids. Compared with terrestrial and saprophytic orchids, epiphytic orchids experienced greater strength of positive selection, with expansion events mostly related to the CslD subfamily, which might have resulted in strong adaptability to stress in epiphytes. Experiments on stem expression changes under abiotic stress showed that the CslA might be a key subfamily in response to drought stress for orchids with different life forms, whereas the CslD might be a key subfamily in epiphytic and saprophytic orchids to adapt to freezing stress. This study provides the basic knowledge for the further systematic study of the adaptive evolution of the CesA/Csl superfamily in angiosperms with different life forms, and research on orchid-specific functional genes related to life-history trait evolution.

New Insights into Artesunate as a Pleiotropic Regulator of Innate and Adaptive Immune Cells.

Artesunate, one of the derivatives of artemisinin ("qinghaosu" in Chinese), is known as an antimalarial drug with high efficiency and low toxicity. Of interest, emerging evidences suggest that artesunate also possesses an immunomodulatory effect during innate and adaptive immune responses in cell types and context-dependent manner. Although it shows promising application in many diseases, such as inflammatory diseases, hypersensitivity, autoimmune diseases, and cancers, little is known about underlying molecular. In this review, we summarize recent advances of how artesunate regulates innate and adaptive immune cells. In addition, its potential application in immune-related diseases is also highlighted.

A water-stable metal-organic framework of a zwitterionic carboxylate with dysprosium: a sensing platform for Ebolavirus RNA sequences.

We herein report a water-stable 3D dysprosium-based metal-organic framework (MOF) that can non-covalently interact with probe ss-DNA. The formed system can serve as an effective fluorescence sensing platform for the detection of complementary Ebolavirus RNA sequences with the detection limit of 160 pM.

Transcriptome comparison reveals candidate genes responsible for the betalain-/anthocyanidin-production in bougainvilleas.

The occurrence of betalains and anthocyanins is mutually exclusive, which is a curious phenomenon in the plant kingdom, and the biochemical mechanisms for this restriction are unknown. In the present study, we performed transcriptome analysis of two betalain-producing species, red Bougainvillea glabra Choisy. 'Sanderiana' (R) and white B. glabra 'Alba' (W) by transcriptome sequencing. In total, we obtained 69692 (Red) and 60727 (White) genes with an average length of 665 and 728bp respectively. Out of 3106 significantly differentially-expressed genes (71%), 1003 were R-specific (32%), and 1605 were W-specific (52%). To validate betalain-/anthocyanidin-biosynthesis genes detected (cytochrome P 450 76AD1 (CYP76AD1), dihydroxy-phenylalanine (DOPA)-4,5-dioxygenase (DODA), cyclo DOPA-5-O-glycosyltransferase (cyclo-DOPA-5-GT) dihydroflavonol 4-reductase (DFR), leucoanthocyanidin dioxygenase (LDOX)), real-time PCR was performed in leaves and three development stages of flowers in four Bougainvilleas, red R, white W, orange Bougainvillea×buttiana 'Salmoea' (O) and purple B. glabra 'Formosa' (P). Contents of betalains were also measured. The results showed that betalains accumulation was consistent with the expression level of DODA in O. A correlation between expression of CYP76AD1 and cyclo-DOPA-5GT and betalains was not discovered. This suggests that production of betacyanins was under the regulation of more complex factors. Both DFR and LDOX responsible for anthocyanidin production were first validated in floral organs and leaves in betalain-producing plants by real-time PCR. These findings suggest a fully functioning anthocyanin pathway, at least, to the stage of LDOX in bougainvilleas.