Visual analysis of the research frontiers, hotspots and trends of exercise therapy intervention in tumor-related sleep-wake disorders.

Objective: To systematically understand the research frontiers, hotspots and development trends of exercise therapy in the intervention of tumor-related sleep-wake disorders, and to provide scientific basis for follow-up research. Methods: Downloaded the original research papers on February 26, 2024, from the Web of Science core collection database, on tumor-associated sleep-wake disorders. The data that met the inclusion criteria were imported into the Bibliometric Analysis Platform (http://biblimetric.com), CiteSpace 6.3.R1 and VOSviwer1.6.20 software for visual analysis, and imported into Excel2021. Scientometric analysis was performed with Oringin2021 and PyCharm Community Edition 2022.1.3. Results: A total of 512 original research papers on tumor-related sleep-wake disorders were obtained. The most influential countries in the subject area are the United States, Spain and German, the institutions are the University of California System, Sun Yat Sen University and Northwestern University, et al., the authors are Berger AM, Aaronson NK, Bower JE, et al., and the journals are Cancer, Brit J Cancer and Cancer Nurs. The co-cited references suggest that the current research frontier in the field mainly involves the level, place and program of exercise therapy, including the relationship between physical activity, sedentary behavior and cancer prevention and control. The results of co-occurrence keyword network analysis showed that quality of life, physical activity, breast cancer, exercise, fatigue, and survivors may be the research hotspots in this field, with breast cancer, health, aerobic exercise, adults, and chemotherapy being the most popular. Conclusions: The number of papers published and the research enthusiasm in this field show a steady upward trend. However, there is a lack of influential institutions and scholars, and there is relatively little research collaboration across countries/regions/institutions. The scientific research influence of institutions and scholars in most European and American countries/regions is significantly ahead of that of institutions and scholars in Asian and African countries/regions. But Sun Yat Sen University in China is a relatively active and influential scientific research institution in recent years, which is worthy of attention. In addition, the research frontier of this discipline is the level, place and program of exercise therapy auxiliary intervention, and the research hotspots involve breast cancer, health, aerobic exercise, adults, chemotherapy, et al. Their clinical efficacy needs to be further demonstrated in multi-center, large-sample and high-quality prospective studies.

Assessment of cognitive dysfunction and its influencing factors after acute ischemic stroke.

OBJECTIVE: In order to provide a more accurate and effective basis for clinical diagnosis and treatment, patients with cognitive dysfunction after acute ischemic stroke (AIS) were evaluated and their influencing factors were analyzed. METHODS: A rigorous and systematic logistic regression analysis was conducted to comprehensively investigate the various influencing factors that contribute to cognitive dysfunction. RESULTS: Among them, the sex granulocyte/lymphocyte ratio (NLR), low-density lipoprotein cholesterol (LDL-C) level, and C-reactive protein (CRP) were also higher than those in the control group (p < 0.05). The scores of memory, orientation, visual and spatial function, abstract thinking and language in the control group were higher than those in the experimental group (p < 0.05). The results of multivariate logistic regression analysis showed that history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking and temporal lobe infarction were risk factors for cognitive dysfunction after AIS, while elevated BMI and love of exercise were protective factors for cognitive dysfunction after AIS. CONCLUSION: Patients with cognitive dysfunction had the highest incidence of temporal lobe infarction, and they scored lower than the control group on memory, orientation, visual and spatial function, abstract thinking, and language function. Multivariate logistic regression analysis showed that a history of diabetes mellitus, high NLR, high LDL-C, high CRP, smoking, and temporal lobe infarction were independent risk factors for cognitive dysfunction after acute ischemic stroke, while elevated BMI and a love of exercise were protective factors for cognitive dysfunction after acute ischemic stroke.

Adipose-derived stem cells ameliorate radiation-induced lung injury by activating the DDAH1/ADMA/eNOS signaling pathway.

Background: Ionizing radiation-induced lung injury is caused by the initial inflammatory reaction and leads to advanced fibrosis of lung tissue. Adipose-derived stem cells (ASCs) are a type of mesenchymal stem cell that can differentiate into various functional cell types with broad application prospects in the treatment of tissue damage. The purpose of this study was to explore the protective effect of ASCs against radiation-induced lung injury and to provide a novel basis for prevention and treatment of radiation-induced lung injury. Materials and methods: Fifty mice were randomly divided into a control group (Ctrl), radiation exposure group (IR), radiation exposure plus ASC treatment group (IR + ASC), radiation exposure plus L-257 group (IR + L-257), and radiation exposure plus ASC treatment and L-257 group (IR + ASC + L-257). Mice in IR, IR + ASC, and IR + ASC + L-257 groups were exposed to a single whole-body dose of 5 Gy X-rays (160 kV/25 mA, 1.25 Gy/min). Within 2 h after irradiation, mice in IR + ASC and IR + ASC + L-257 groups were injected with 5 × 106 ASCs via the tail vein. Mice in IR + L-257 and IR + ASC + L-257 groups were intraperitoneally injected with 30 mg/kg L-257 in 0.5 mL saline. Results: The mice in the IR group exhibited lung hemorrhage, edema, pulmonary fibrosis, and inflammatory cell infiltration, increased release of proinflammatory cytokines, elevation of oxidative stress and apoptosis, and inhibition of the dimethylarginine dimethylamino hydratase 1 (DDAH1)/ADMA/eNOS signaling pathway. ASC treatment alleviated radiation-induced oxidative stress, apoptosis, and inflammation, and restored the DDAH1/ADMA/eNOS signaling pathway. However, L-257 pretreatment offset the protective effect of ASCs against lung inflammation, oxidative stress, and apoptosis. Conclusions: These data suggest that ASCs ameliorate radiation-induced lung injury, and the mechanism may be mediated through the DDAH1/ADMA/eNOS signaling pathway.

Extraction and analysis of high-quality chloroplast DNA with reduced nuclear DNA for medicinal plants.

BACKGROUND: Obtaining high-quality chloroplast genome sequences requires chloroplast DNA (cpDNA) samples that meet the sequencing requirements. The quality of extracted cpDNA directly impacts the efficiency and accuracy of sequencing analysis. Currently, there are no reported methods for extracting cpDNA from Erigeron breviscapus. Therefore, we developed a suitable method for extracting cpDNA from E. breviscapus and further verified its applicability to other medicinal plants. RESULTS: We conducted a comparative analysis of chloroplast isolation and cpDNA extraction using modified high-salt low-pH method, the high-salt method, and the NaOH low-salt method, respectively. Subsequently, the number of cpDNA copies relative to the nuclear DNA (nDNA ) was quantified via qPCR. As anticipated, chloroplasts isolated from E. breviscapus using the modified high-salt low-pH method exhibited intact structures with minimal cell debris. Moreover, the concentration, purity, and quality of E. breviscapus cpDNA extracted through this method surpassed those obtained from the other two methods. Furthermore, qPCR analysis confirmed that the modified high-salt low-pH method effectively minimized nDNA contamination in the extracted cpDNA. We then applied the developed modified high-salt low-pH method to other medicinal plant species, including Mentha haplocalyx, Taraxacum mongolicum, and Portulaca oleracea. The resultant effect on chloroplast isolation and cpDNA extraction further validated the generalizability and efficacy of this method across different plant species. CONCLUSIONS: The modified high-salt low-pH method represents a reliable approach for obtaining high-quality cpDNA from E. breviscapus. Its universal applicability establishes a solid foundation for chloroplast genome sequencing and analysis of this species. Moreover, it serves as a benchmark for developing similar methods to extract chloroplast genomes from other medicinal plants.

[Chidamide Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells from Patients with Myelodysplastic Syndromes].

OBJECTIVE: To explore the effects and mechanisms of chidamide on the osteogenic differentiation of bone marrow mesenchymal stromal cells (MSC) from myelodysplastic syndromes (MDS). METHODS: MSC were isolated and cultured from bone marrow of MDS patients and healthy donors. CCK-8 assay was used to detect the effects of chidamide on the proliferation of MSC. The effects of chidamide on the activity of histone deacetylase (HDAC) in MSC was measured by a fluorescence assay kit and Western blot. Alkaline phosphatase (ALP) activity was detected on day 3 and calcium nodule formation was observed by Alizarin Red staining on day 21 after osteogenic differentiation. The expression of early and late osteogenic genes was detected on day 7 and day 21, respectively. RT-PCR and Western blot were used to detect the effects of chidamide on mRNA and protein expression of RUNX2 which is the key transcription factor during osteogenesis. RESULTS: As the concentration of chidamide increased, the proliferation of MSC was inhibited. However, at a low concentration (1 µmol/L), chidamide had no significant inhibitory effect on MSC proliferation but significantly inhibited HDAC activity. In MSC from both MDS patients and healthy donors, chidamide (1 µmol/L) significantly increased ALP activity, calcium nodule formation, thereby mRNA expression of osteogenic genes, and restored the reduced osteogenic differentiation ability of MDS-MSC compared to normal MSC. Mechanistic studies showed that the osteogenic-promoting effect of chidamide may be related to the upregulation of RUNX2 . CONCLUSION: Chidamide can inhibit HDAC activity in MSC, upregulate the expression of the osteogenic transcription factor RUNX2, and promote the osteogenic differentiation of MDS-MSC.

Opening the black box: explainable deep-learning classification of wood microscopic image of endangered tree species.

BACKGROUND: Traditional method of wood species identification involves the use of hand lens by wood anatomists, which is a time-consuming method that usually identifies only at the genetic level. Computer vision method can achieve "species" level identification but cannot provide an explanation on what features are used for the identification. Thus, in this study, we used computer vision methods coupled with deep learning to reveal interspecific differences between closely related tree species. RESULT: A total of 850 images were collected from the cross and tangential sections of 15 wood species. These images were used to construct a deep-learning model to discriminate wood species, and a classification accuracy of 99.3% was obtained. The key features between species in machine identification were targeted by feature visualization methods, mainly the axial parenchyma arrangements and vessel in cross section and the wood ray in tangential section. Moreover, the degree of importance of the vessels of different tree species in the cross-section images was determined by the manual feature labeling method. The results showed that vessels play an important role in the identification of Dalbergia, Pterocarpus, Swartzia, Carapa, and Cedrela, but exhibited limited resolutions on discriminating Swietenia species. CONCLUSION: The research results provide a computer-assisted tool for identifying endangered tree species in laboratory scenarios, which can be used to combat illegal logging and related trade and contribute to the implementation of CITES convention and the conservation of global biodiversity.

Hai-Honghua medicinal liquor is a reliable remedy for fracture by promotion of osteogenic differentiation via activation of PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hai-Honghua medicinal liquor (HHML), an external Chinese herbal formula preparation, is often applied to treat freshly closed tibia/fibular fractures, ankle fractures, and other bone-related disorders, but the related molecular mechanism is unclear. AIM OF THE STUDY: To evaluate the therapeutic effect of HHML in patients with tibial/fibular and ankle fractures, and to explore its related possible mechanism. METHODS AND MATERIALS: A total of 182 patients with tibia/fibular fractures and 183 patients with ankle fractures were enrolled in this study. A randomized, controlled, unblinded clinical trial was designed to evaluate the therapeutic effect of HHML on tibial/fibular and ankle fractures. The chemical compositions of HHML were analyzed by the HPLC-Q-Extractive MS/MS. Furthermore, a rat tibial fracture model was established to evaluate the therapeutic effects of HHML in promoting fracture healing, and the mouse embryonic osteoblasts cell line of MC3T3-E1 was further carried out to explore the mechanisms of HHML on osteoblast differentiation. RESULTS: In the clinical evaluation, HHML treatment significantly shortened the time for pain and swelling in patients with tibial/fibular fractures (P < 0.01) and ankle fractures (P < 0.01), and the incidence of complications was significantly reduced as well. Subsequently, 116 constituents were identified from HHML via HPLC-Q-TOF-MS/MS analysis. In vivo, no obvious changes in weight were observed in HHML-treated rats. Moreover, the levels of bone formation markers (including osteocalcin (OCN), N-terminal propeptide of type I procollagen (PINP), alkaline phosphatase (ALP), calcium (Ca) and substance P) in rat serum were significantly increased in HHML-treated rats compared with model rats (P < 0.05). Micro-CT analysis showed bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th) of the HHML-treated rats were significantly increased (P < 0.05, vs. Model) while trabecular separation (Tb.Sp) and structure model index (SMI) values were significantly reduced (P < 0.05, vs. Model). Histological analysis showed that HHML treatment promoted the healing of fractures and cartilage repair, and increased the osteoblasts and collagen fibers. Furthermore, our results also revealed HHML could promote MC3T3-E1 cells proliferation and osteoblast differentiation via regulation of the runt-related transcription factor 2 (RUNX2), bone alkaline phosphatase (BALP), and OCN by activating phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, which confirmed by adding PI3K chemical inhibitor of LY294002. CONCLUSION: HHML treatment is a reliable remedy for fractures in tibial and ankle by promotion of osteogenic differentiation via activation of PI3K/Akt pathway.

Polyvinyl alcohol/kappa-carrageenan-based package film with simultaneous incorporation of ferric ion and polyphenols from Capsicum annuum leaves for fruit shelf-life extension.

Bio-based food packaging materials have elicited growing interests due to their great degradability, high safety and active biofunctions. In this work, by simultaneously introducing the polyphenolic extracts from Capsicum annuum leaves and ferric ion (Fe3+) into the Polyvinyl alcohol/kappa-carrageenan (PVA/κ-carrageenan)-based film-forming matrix, an active package film was developed, with the purpose to improve the food shelf life. The experimental results indicated that the existence of Fe3+ can not only improve the mechanical properties owing to the multiple dynamic coordinated interactions, but also endow the composite films with excellent fire-retardancy. Moreover, the composite films could display excellent UV resistant performance, water vapor/oxygen gas barrier properties and antioxidant activities with the corporation of polyphenols. In particular, the highest DPPH and ABTS radical scavenging capacities for composite film (PC-PLP7 sample) were evaluated to be 82.5 % and 91.1 %, respectively. Higher polyphenol concentration is favorable to the bio-functions of the materials. Benefitting from these features, this novel kind of films with a dense and steady micro-structure could be further applicated in fruit preservations, where the ripening bananas were ensured with the high storage quality. This integration as a prospective food packaging material provides an economic and eco-friendly approach to excavate the high added-values of biomass.

A Prenyltransferase Participates in the Biosynthesis of Anthraquinones in Rubia cordifolia.

Anthraquinones constitute the largest group of natural quinones, which are used as safe natural dyes and have many pharmaceutical applications. In plants, anthraquinones are biosynthesized through two main routes: the polyketide pathway and the shikimate pathway. The latter primarily forms alizarin-type anthraquinones, and the prenylation of 1,4-dihydroxy-2-naphthoic acid is the first pathway-specific step. However, the prenyltransferase responsible for this key step remains uncharacterized. In this study, the cell suspension culture of Madder (Rubia cordifolia), a plant rich in alizarin-type anthraquinones, was discovered to be capable of prenylating 1,4-dihydroxy-2-naphthoic acid to form 2-carboxyl-3-prenyl-1,4-naphthoquinone and 3-prenyl-1,4-naphthoquinone. Then, a candidate gene belonging to the UbiA superfamily, R. cordifolia  dimethylallyltransferase 1 (RcDT1), was shown to account for the prenylation activity. Substrate specificity studies revealed that the recombinant RcDT1 recognized naphthoic acids primarily, followed by 4-hydroxyl benzoic acids. The prenylation activity was strongly inhibited by 1,2- and 1,4-dihydroxynaphthalene. RcDT1 RNA interference significantly reduced the anthraquinones content in R. cordifolia callus cultures, demonstrating that RcDT1 is required for alizarin-type anthraquinones biosynthesis. The plastid localization and root-specific expression further confirmed the participation of RcDT1 in anthraquinone biosynthesis. The phylogenetic analyses of RcDT1 and functional validation of its rubiaceous homologs indicated that DHNA-prenylation activity evolved convergently in Rubiaceae via recruitment from the ubiquinone biosynthetic pathway. Our results demonstrate that RcDT1 catalyzes the first pathway-specific step of alizarin-type anthraquinones biosynthesis in R. cordifolia. These findings will have profound implications for understanding the biosynthetic process of the anthraquinone ring derived from the shikimate pathway.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents.

The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 µM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.

Characterization of CYP82 genes involved in the biosynthesis of structurally diverse benzylisoquinoline alkaloids in Corydalis yanhusuo.

Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.

Clinical characteristics of Guillain-Barré syndrome in patients with primary Sjögren's syndrome.

To investigate the clinical characteristics of Guillain-Barré syndrome (GBS) in patients with primary Sjögren's syndrome (SS). Records of patients with positive anti-SSA antibodies hospitalized in the Beijing Tiantan Hospital between December 2011 and May 2020 were retrieved. Patients who fulfilled the criteria for diagnosis of GBS and primary SS were included, and their clinical data were analyzed. Among the 785 patients with positive anti-SSA, 52 patients were identified in this study. They were 27 males and 25 females with median age of 59 years old. Besides anti-SSA antibodies, multiple autoantibodies were detected in these patients including antinuclear antibody, anti-Ro52, anti-mitochondrial M2, anti-thyroid peroxidase and anti-thyroglobulin autoantibodies. Preceding infection was reported in 42 patients. Hyporeflexia/areflexia and limbs weakness were the most common manifestation and 35 patients presented cranial nerve injuries. GBS disability score of 3, 4 and 5 was scaled in 28 (53.8%), 15 (28.8%) and 3 (5.8%) patients respectively. Forty-six patients received intravenous immunoglobulin (IVIG) monotherapy, 5 patients were treated by IVIG plus glucocorticoids, and 51 patients improved during hospitalization. The frequency of male gender among the patients with both GBS and primary SS suggests an independent onset of GBS and the co-existence of these autoimmune diseases in patients with multiple autoantibodies. Majority of patients with GBS and primary SS experience benign disease course.

The clinical characteristics, gene mutations and outcomes of myelodysplastic syndromes with diabetes mellitus.

PURPOSE: Diabetes mellitus (DM) is the second most common comorbidity in myelodysplastic syndromes (MDS). The purpose of the study was to investigate the clinical characteristics of MDS patients with DM. METHODS: A retrospective analysis was performed on the clinical data of 890 MDS patients with or without DM. Clinical data, including genetic changes, overall survival (OS), leukemia-free survival (LFS) and infection, were analyzed. RESULTS: Among 890 patients, 184 (20.7%) had DM. TET2 and SF3B1 mutations occurred more frequently in the DM group than those in the non-DM group (p = 0.0092 and p = 0.0004, respectively). Besides, DM was an independent risk factor for infection (HR 2.135 CI 1.451-3.110, p = 0.000) in MDS. Compared to non-DM patients, MDS patients with DM had poor OS and LFS (p = 0.0002 and p = 0.0017, respectively), especially in the lower-risk group. While in multivariate analysis, DM did not retain its prognostic significance and the prognostic significance of infection was maintained (HR 2.488 CI 1.749-3.538, p = 0.000). CONCLUSIONS: MDS patients with DM have an inferior prognosis which may due to higher infection incidence, with TET2 and SF3B1 mutations being more frequent in those cases.

Identification and Functional Mechanism Verification of Novel MicroRNAs Associated with the Fibrosis Progression in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a serious threat to human health worldwide, and its incidence is increasing annually. A growing amount of information is emerging about the role of micoRNAs (miRNAs) in the regulation of renal fibrosis, which has aroused interest in the development of drugs that block pathogenic miRNAs or restore protective miRNAs levels. To clarify the role of miRNAs in CKD, we selected patients with significant renal fibrotic disease (diabetic nephropathy (DN) and focal segmental glomerulosclerosis (FSGS)) as the disease group, and patients with little or no renal fibrotic disease (minimal change disease (MCD) and renal carcinoma adjacent to normal kidney) as controls. Significantly differentially expressed miRNAs were obtained by human kidney tissue sequencing, subsequently verified in mice models of DN and FSGS, and subsequently inhibited or overexpressed in human renal tubular epithelial cells (HK-2) stimulated by high glucose (HG) and TGF-ß1 in vitro. Therefore, the mechanism of its action in renal fibrosis was further elaborated. Finally, the downstream target genes of the corresponding miRNAs were verified by bioinformatics analysis, qRT-PCR, western blot and double luciferase report analysis. Two novel miRNAs, hsa-miR-1470-3p (miR-1470) and hsa-miR-4483-3p (miR-4483), were detected by renal tissue sequencing in the disease group with significant renal fibrosis (DN and FSGS) and the control group with little or no renal fibrosis (MCD and normal renal tissue adjacent to renal carcinoma). Subsequent human renal tissue qRT-PCR verified that the expression of miR-1470 was significantly increased, while the expression of miR-4483 was markedly decreased in the disease group (p < 0.05). Moreover, in vivo DN and FSGS mice models, the expression levels of miR-1470 and miR-4483 were consistent with the results of human kidney tissue. In vitro, miR-4483 was suppressed, whereas miR-1470 was induced by treatment with TGF-ß1 or HG. Inhibition of miR-1470 or overexpression of miR-4483 promoted HG or TGF-ß1-induced fibrosis in HK-2 cells. Further study revealed that MMP-13 and TIMP1 were the target genes ofmiR-1470 and miR-4483, respectively. Our study identifies newly dysregulated miRNA profiles related to fibrosis kidneys. miR-1470 and miR-4483 are demonstrated to participate in kidney fibrosis by regulation of MMP-13, TIMP1 respectively. Our results may represent a promising research direction for renal disorders and help identify new biomarkers and therapeutic targets for CKD.

Analyses of high spatial resolution datasets identify genes associated with multi-layered secondary cell wall thickening in Pinus bungeana.

BACKGROUND AND AIMS: Secondary cell wall (SCW) thickening is a major cellular developmental stage determining wood structure and properties. Although the molecular regulation of cell wall deposition during tracheary element differentiation has been well established in primary growth systems, less is known about the gene regulatory processes involved in the multi-layered SCW thickening of mature trees. METHODS: Using third-generation [long-read single-molecule real-time (SMRT)] and second-generation [short-read sequencing by synthesis (SBS)] sequencing methods, we established a Pinus bungeana transcriptome resource with comprehensive functional and structural annotation for the first time. Using these approaches, we generated high spatial resolution datasets for the vascular cambium, xylem expansion regions, early SCW thickening, late SCW thickening and mature xylem tissues of 71-year-old Pinus bungeana trees. KEY RESULTS: A total of 79 390 non-redundant transcripts, 31 808 long non-coding RNAs and 5147 transcription factors were annotated and quantified in different xylem tissues at all growth and differentiation stages. Furthermore, using this high spatial resolution dataset, we established a comprehensive transcriptomic profile and found that members of the NAC, WRKY, SUS, CESA and LAC gene families are major players in early SCW formation in tracheids, whereas members of the MYB and LBD transcription factor families are highly expressed during late SCW thickening. CONCLUSIONS: Our results provide new molecular insights into the regulation of multi-layered SCW thickening in conifers. The high spatial resolution datasets provided can serve as important gene resources for improving softwoods.

Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex.

Background: The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown. This study was designed to investigate the involvement of the cerebello-thalamus-motor cortical loop mediating consciousness transitions from the loss of consciousness (LOC) induced by an inhalational anesthetic sevoflurane in mice. Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used to investigate the potential link among cerebello-thalamus-motor cortical brain regions. The fiber photometry of calcium and neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) and norepinephrine (NE), were monitored from the motor cortex (M1) and the 5th lobule of the cerebellar vermis (5Cb) during unconsciousness induced by sevoflurane and gaining consciousness after sevoflurane exposure. Cerebellar Purkinje cells were optogenetically manipulated to investigate their influence on consciousness transitions during and after sevoflurane exposure. Results: Activation of 5Cb Purkinje cells increased the Ca2+ flux in the M1 CaMKIIα+ neurons, but this increment was significantly reduced by inactivation of posterior and parafascicular thalamic nucleus. The 5Cb and M1 exhibited concerted calcium flux, and glutamate and GABA release during transitions from wakefulness, loss of consciousness, burst suppression to conscious recovery. Ca2+ flux and Glu release in the M1, but not in the 5Cb, showed a strong synchronization with the EEG burst suppression, particularly, in the gamma-band range. In contrast, the Glu, GABA and NE release and Ca2+ oscillations were coherent with the EEG gamma band activity only in the 5Cb during the pre-recovery of consciousness period. The optogenetic activation of Purkinje cells during burst suppression significantly facilitated emergence from anesthesia while the optogenetic inhibition prolonged the time to gaining consciousness. Conclusions: Our data indicate that cerebellar neuronal communication integrated with motor cortex through thalamus promotes consciousness recovery from anesthesia which may likely serve as arousal regulation.

Cerebral Mechanism of Tuina on the Descending Pain Inhibitory System in Knee Osteoarthritis: Protocol for a Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is reputedly the most common musculoskeletal disease of the lower limbs and the main cause of pain and disability among older individuals. Pain is the most significant and widespread symptom of KOA. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. Crucially, the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission. Tuina, a manual therapy, is effective and safe for reducing clinical symptoms of KOA; however, the mechanism that influences pain through the descending pain inhibitory system in KOA is unclear. OBJECTIVE: This study aims to investigate the modulatory implications of Tuina on the RVM and PAG, which have critical roles in the descending pain inhibitory system in patients with KOA. METHODS: This randomized controlled parallel trial will be conducted at the Tuina Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine (Zhengzhou, China). Patients with KOA will be randomly assigned (1:1) to 6 weeks of health education or Tuina. All patients in both groups will accept a resting-state functional magnetic resonance scan at the beginning and end of the experiment, and the resting-state functional connectivity and the voxel-based morphometry analysis will be performed to detect the RVM and PAG function and structure changes. The clinical outcome assessments will be (1) the pressure pain thresholds, (2) the Numerical Rating Scale, (3) the Hamilton Depression Scale (HAMD), and (4) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Considering that this trial is a study of resting-state functional magnetic resonance imaging technology, resting-state functional connectivity and voxel-based morphometry are the primary outcomes, and clinical outcome assessments are secondary outcomes. Adverse events will be documented and assessed throughout. All main analyses will be carried out on the basis of the intention-to-treat principle. The outcome evaluators and data statisticians will be masked to the treatment group assignment to reduce the risk of bias. RESULTS: This trial was approved by the ethics committee of the Third Affiliated Hospital of Henan University of Chinese Medicine. Enrollment began in December 2023, and the results of this trial are expected to be submitted for publication in May 2025. CONCLUSIONS: This trial will identify a possible relationship between function and structure changes of RVM and PAG and the improvement of clinical variables, elucidating the effect of Tuina on the descending pain inhibitory system of patients with KOA. This trial will provide much-needed knowledge for Tuina for patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070289; https://www.chictr.org.cn/showproj.html?proj=182570. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52820.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Engineered Peptides Harboring Cation Motifs Against Multidrug-Resistant Bacteria.

Multidrug-resistant (MDR) pathogens pose a serious threat to the health and life of humans, necessitating the development of new antimicrobial agents. Herein, we develop and characterize a panel of nine amino acid peptides with a cation end motif. Bioactivity analysis revealed that the short peptide containing "RWWWR" as a central motif harboring mirror structure "KXR" unit displayed not only high activity against MDR planktonic bacteria but also a clearance rate of 92.33% ± 0.58% against mature biofilm. Mechanically, the target peptide (KLR) killed pathogens by excessively accumulating reactive oxygen species and physically disrupting membranes, thereby enhancing its robustness for controlling drug resistance. In the animal model of sepsis infection by MDR bacteria, the peptide KLR exhibited strong therapeutic effects. Collectively, this study provided the dominant structure of short antimicrobial peptides (AMPs) to replenish our arsenals for combating bacterial infections and illustrated what could be harnessed as a new agent for fighting MDR bacteria.

Prevalence and adverse perinatal outcomes of anaemia in the third trimester of pregnancy in Hebei Province, China.

BACKGROUND: Anaemia in pregnancy is one of the most frequent complications related to pregnancy and is a public health concern. This article examines the prevalence of anaemia in the third trimester of pregnancy and the associations between anaemia and adverse perinatal outcomes in Hebei Province, China. METHODS: We used SPSS software to describe the incidence of anaemia in the third trimester of pregnancy in Hebei Province and analysed the clinical characteristics in anaemic patients and the relationship between anaemia and adverse pregnancy outcomes. RESULTS: The overall prevalence of anaemia in the third trimester of pregnancy was 35.0% in Hebei Province. The prevalence of anaemia in the population with a high education level was lower than that in the population with a low education level. The incidence rate in rural areas was higher than that in urban areas. After adjustment for confounding factors, anaemia in the third trimester of pregnancy is an independent risk factor in terms of placenta previa, placental abruption, uterine atony, pre-eclampsia, gestational diabetes mellitus, heart disease, postpartum haemorrhage, premature birth, laceration of birth canal, puerperal infection, caesarean section and large for gestational age. CONCLUSIONS: The prevalence of anaemia in the third trimester of pregnancy is associated with an increased risk of adverse perinatal outcomes. A comprehensive approach to prevent anaemia is needed to improve maternal and child health outcomes.