Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery.

The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P < 0.001). Staphylococcus epidermidis was the major pathogen in the conjunctival sac before corneal refractive surgery, and the culture positivity rate of the conjunctival bacteria was higher in males. Sixteen of 37 eyes (43.2%) with contact lenses had positive culture results, compared to 33 of 61 eyes (54.1%) without contact lenses (P > 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

[Characteristics of Soil Organic Carbon and Its Influencing Factors of Different Plant Communities in the Yellow River Delta].

Changes in soil organic carbon （SOC） are of great importance to the evolution of soil quality. The distribution characteristics of soil organic carbon （SOC）, easily oxidizable organic carbon （EOC）, dissolved organic carbon （DOC）, and particulate organic carbon （POC） were investigated in the 0-50 cm soil layer of the Phragmites australis, Suaeda salsa, and Tamarix chinensis communities of the supratidal zone in the Yellow River Delta as the research subjects. Then, the composition and sources of soil dissolved organic matter （DOM） were analyzed based on the UV-vis spectroscopy, three-dimensional excitation emission matrix spectroscopy, and parallel factor analysis （PARAFAC）. Finally, the key factors affecting the characteristics of soil organic carbon and DOM fractions of different plant communities were finally revealed in combination with the physicochemical properties of the soil. The results showed that： ① Comparing different communities, the S. salsa community had the highest ω（SOC） at 7.53 g·kg-1, the T. chinensis community had the highest ω（DOC） at 0.98 g·kg-1, and the P. australis community had significantly higher ω（EOC） and ω（POC） than those of the S. salsa and T. chinensis communities at 1.47 g·kg-1 and 0.65 g·kg-1, respectively. The vertical distribution showed a tendency to decrease with deeper soil layers, except for POC concentration. ② The main components of soil DOM of the P. australis, S. salsa, and T. chinensis communities were humus, protein-like substances, and fulvic acid-like substances, of which exogenous components accounted for 55.80%, 56.41%, and 52.81% in the above communities, respectively. ③ Comparing different communities, the humification degree of the P. australis community was significantly higher than that of the S. salsa and T. chinensi communities, but its aromaticity and proportion of biological sources were significantly lower than those of the T. chinensi community. On the vertical profile of the soil, DOM aromaticity and humification degree gradually increased with the deepening of the soil layer, and the deeper soils were mainly dominated by small molecular weight DOM with a lower proportion of hydrophobic fraction. ④ Redundant analysis showed that N （P<0.01）, NO2--N （P<0.01）, and NH4+-N （P<0.05） were the key factors affecting the changes in soil organic carbon and DOM fractions.

Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury.

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.

Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain.

Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin's analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin's efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin's analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation-key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy.

Experimental Study on the Effect of Polycarboxylate Superplasticizer on the Performance of Cement-Based Grouting Materials.

Polycarboxylate superplasticizers BMC-L and BMC-S were utilized as modifiers in the formulation of novel cement-based grouting materials. Indoor tests were conducted on 32 groups of cement slurries, varying by water-cement ratio (0.5:1 and 0.6:1) and modifier content (0, 2‱, 4‱, 6‱, 8‱, 10‱, 12‱, and 14‱), to test their density, funnel viscosity, water separation rate, and stone rate. Four groups of slurry modified with BMC-L were selected as the preferred slurry, and the apparent viscosity test, uniaxial, and triaxial compression test of the slurry stone body were conducted. The study investigated the influence of BMC-L on various properties of the slurry, including its apparent viscosity, uniaxial compressive strength, stress-strain relationships, shear strength parameters, and elastic modulus. Ultimately, the pore structure and phase composition of the slurry stone body were detected by Nuclear Magnetic Resonance (NMR) and X-ray Diffraction (XRD), and the impact of BMC-L on slurry performance was examined from a microstructural perspective. Results indicate that the two polycarboxylate superplasticizers exert minimal influence on the density and water separation rate of the slurry. Within the effective incorporation range of the polycarboxylate superplasticizer, increasing the dosage correlates with a decrease in both the stone rate and viscosity of the slurry. BMC-L significantly enhances the mechanical properties of the slurry stone body by promoting more complete cement hydration and reducing porosity. The uniaxial compressive strength of slurry stone body with a 6 ‱ BMC-L dosage reached 29.7 MPa after 7 days and 38.5 MPa after 28 days of curing, representing increases of 118.4% and 64%, respectively, compared to masonry with 0 BMC-L dosage. The shear strength parameters and elastic modulus of the slurry stone body also showed corresponding increases.

Nonreciprocal routing of microwave photons with broad bandwidth via magnon-cavity chiral coupling.

We propose a scheme for realizing nonreciprocal microwave photon routing with two cascaded magnon-cavity coupled systems, which work around the exceptional points of a parity-time (PT)-symmetric Hamiltonian. An almost perfect nonreciprocal transmission can be achieved with a broad bandwidth, where the transmission for a forward-propagating photon can be flexibly controlled with the backpropagating photon being isolated. The transmission or isolated direction can be reversed via simply controlling the magnetic field direction applied to the magnons. The isolation bandwidth is improved by almost three times in comparison with the device based on a single PT-symmetric system. Moreover, the effect of intrinsic cavity loss and added thermal noises is considered, confirming the experimental feasibility of the nonreciprocal device and potential applications in quantum information processing.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Layered Composite Dorsal Onlay Implant for Augmentation Rhinoplasty.

The use of autologous costal cartilage in augmentation rhinoplasty is well-established. However, scenarios where costal cartilage is insufficient or patients are unwilling to undergo additional cartilage harvesting present a challenge. This study introduces a composite dorsal onlay implant, combining silicone and costal cartilage, as an effective solution. Twenty female patients were enrolled in this study. Of these patients, 8 underwent revision surgery who had previous rhinoplasty with costal cartilage graft, and 12 had never previously undergone surgery involving the harvesting of costal cartilage. The implant, created by suturing a silicone base with a costal cartilage overlay, demonstrated low rates of warping and translucency over a mean follow-up of 11.4 months. This method offers a refined nasal appearance, particularly a higher dorsum with reduced translucency for patients with limited costal cartilage availability.

Association of greenspace and natural environment with brain volumes mediated by lifestyle and biomarkers among urban residents.

OBJECTIVES: To examine the associaiton between environmental measures and brain volumes and its potential mediators. STUDY DESIGN: This was a prospective study. METHODS: Our analysis included 34,454 participants (53.4% females) aged 40-73 years at baseline (between 2006 and 2010) from the UK Biobank. Brain volumes were measured using magnetic resonance imaging between 2014 and 2019. RESULTS: Greater proximity to greenspace buffered at 1000 m at baseline was associated with larger volumes of total brain measured 8.8 years after baseline assessment (standardized ß (95% CI) for each 10% increment in coverage: 0.013(0.005,0.020)), grey matter (0.013(0.006,0.020)), and white matter (0.011(0.004,0.017)) after adjustment for covariates and air pollution. The corresponding numbers for natural environment buffered at 1000 m were 0.010 (0.004,0.017), 0.009 (0.004,0.015), and 0.010 (0.004,0.016), respectively. Similar results were observed for greenspace and natural environment buffered at 300 m. The strongest mediator for the association between greenspace buffered at 1000 m and total brain volume was smoking (percentage (95% CI) of total variance explained: 7.9% (5.5-11.4%)) followed by mean sphered cell volume (3.3% (1.8-5.8%)), vitamin D (2.9% (1.6-5.1%)), and creatinine in blood (2.7% (1.6-4.7%)). Significant mediators combined explained 18.5% (13.2-25.3%) of the association with total brain volume and 32.9% (95% CI: 22.3-45.7%) of the association with grey matter volume. The percentage (95% CI) of the association between natural environment and total brain volume explained by significant mediators combined was 20.6% (14.7-28.1%)). CONCLUSIONS: Higher coverage percentage of greenspace and environment may benefit brain health by promoting healthy lifestyle and improving biomarkers including vitamin D and red blood cell indices.

An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

Amygdala neuronal dyshomeostasis via 5-HT receptors mediates mood and cognitive defects in Alzheimer's disease.

Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre- to post-onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5-HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5-HT levels, in which both restrained inhibitory inputs by excessive 5-HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5-HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5-HT receptors simultaneously enables neurons to resist ß-amyloid peptides (Aß) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5-HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline.

The basal forebrain to lateral habenula circuitry mediates social behavioral maladaptation.

Elucidating the neural basis of fear allows for more effective treatments for maladaptive fear often observed in psychiatric disorders. Although the basal forebrain (BF) has an essential role in fear learning, its function in fear expression and the underlying neuronal and circuit substrates are much less understood. Here we report that BF glutamatergic neurons are robustly activated by social stimulus following social fear conditioning in male mice. And cell-type-specific inhibition of those excitatory neurons largely reduces social fear expression. At the circuit level, BF glutamatergic neurons make functional contacts with the lateral habenula (LHb) neurons and these connections are potentiated in conditioned mice. Moreover, optogenetic inhibition of BF-LHb glutamatergic pathway significantly reduces social fear responses. These data unravel an important function of the BF in fear expression via its glutamatergic projection onto the LHb, and suggest that selective targeting BF-LHb excitatory circuitry could alleviate maladaptive fear in relevant disorders.

Phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in pediatric patients.

Corneal dystrophies may develop gradually from early onset in childhood and persist for years to decades. Visual impairment or repeated ocular irritations caused by corneal dystrophies severely affect the quality of life. Although various surgical treatment options are indicated for adult patients, the treatment plan for pediatric patients remains unclear. Herein we describe clinical observations of phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in three pediatric patients (five eyes). Corneal opacities were successfully removed, and visual acuity was greatly improved in all operated eyes. The procedure of phototherapeutic keratectomy seems to be feasible in the treatment of corneal epithelial-stromal dystrophies in c hildren, with advantages of minimal invasion and good visual outcomes.

A study on the application of radiomics based on cardiac MR non-enhanced cine sequence in the early diagnosis of hypertensive heart disease.

BACKGROUND: The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension. METHODS: 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity. RESULTS: The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively. CONCLUSIONS: Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

FoxO3 Regulates Mouse Bone Mesenchymal Stem Cell Fate and Bone-Fat Balance During Skeletal Aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-polymerase chain reaction, Western blot, and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling, respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs and is a potential target for the prevention of age-related osteoporosis.

Plant-LncPipe: a computational pipeline providing significant improvement in plant lncRNA identification.

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.