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Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)‐induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX‐induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX‐induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM‐ and Akk‐induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM‐induced anti‐osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone. Colonization with gut microbiota from children (CGM) but not from the elderly (EGM) reverses the ovariectomy (OVX)‐induced reduction of Akkermansia muciniphila (Akk) and prevents OVX‐induced osteoporosis. Direct replenishment of Akk also induces bone benefits in OVX mice. Extracellular vesicles from CGM and Akk can enter into bone to directly attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenesis and inhibiting osteoclastogenesis.

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aβ). The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aβ levels, neuron numbers (MAP2 ) and activated microglia (CD68 IBA1 ) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes ( ) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aβ in the brain tissues were determined. MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 ( ) and Optineurin ( ), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aβ clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines, accessing analogs capable of mimicking ortho - and meta -substituted anilines remains challenging due to the lack of a versatile and modular synthetic methods. Herein, we present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp 3 )–N Coupling. The success of this reaction hinges on the merging the cooperative ligand-to-metal charge transfer (LMCT) with copper-catalyzed amination. Notably, this net-oxidative C(sp 3 )–N forming reaction operates under mild electrode potentials and proceeds through hydrogen evolution, eliminating the need for external chemical oxidants. Our research enables the facile decarboxylative amination of a set of sp 3 -rich small-ring cage carboxylic acids, thus offering a versatile bioisosteric replacement for ortho -, meta -, and para -substituted anilines and di(hetero)aryl amines. Accessing analogs capable of mimicking ortho- and meta-substituted anilines remains challenging due to the lack of a versatile and modular synthetic method. Here, the authors present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp 3 )–N Coupling.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr ; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2 . Moreover, Cdh5 + BMSCs and Tek + BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5 + TEK + ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5 + BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition. Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.

Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a \"factory\" to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.

The semi-double ( semiplenus ) floral trait is highly valued in the field of horticulture, yet it remains exceptionally rare in wild plants. Rubus semiplenus , a new species with naturally occurring semi-double flowers, is described and illustrated. This new species was discovered in the Nanyue Hengshan National Nature Reserve, Hunan Province, China. It is distinguished by its herbaceous to dwarf subshrub habit, simple suborbicular leaves (0.7–2.5 × 0.7–2.5 cm), and semi-double flowers with dicyclic petals (10–12). Molecular phylogenetic analyses based on ITS and rbc L + mat K sequences consistently confirmed that R. semiplenus belongs to Sect. Rosaefolii as defined by Focke and is closed to R. hirsutus .

Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial–mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.

According to previous guidelines, the lymph nodes around the right side of the superior mesenteric artery (SMA) should be dissected and removed However, due to the technical challenge and the risk of complications, most surgeons perform the dissection along the axis of the superior mesenteric vein (SMV). Herein, we described an 'artery-first' approach for laparoscopic radical extended right hemicolectomy with complete mesocolic excision (CME). A total of 22 cases were collected from January to October 2016. The right side of the SMA and SMV were exposed and separated, and the No. 203, No. 213 and No. 223 lymph nodes were dissected Toldt's fascia was dissected and expanded laterally to the ascending colon, cranial to the pancreas head. The caudal root of the mesentery and lateral attachments of the ascending colon were completely mobilized. There were 9 male and 13 female patients, with a mean age of 63.1 (range, 39-83) years and the mean body mass index was 24.6 (range, 18.3-37.7) kg/m . The mean operative time was 192.5 (range, 145-240) minutes and the mean intra-operative blood loss was 55.0 (range, 10-300) ml. The mean number of harvested lymph nodes was 27.0 (range, 13-55) and the time to flatus and hospital stay were 35.0 (range, 26-120) hours and 7.5 (range, 5-20) days, respectively. Minor complications occurred in two patients and no post-operative death was observed. The preliminary results suggest that the reported approach may be a feasible and safe procedure that is more in accordance with the principles of CME.

ObjectiveNanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy.MethodsWe evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested.ResultsF-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment.ConclusionsF-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.