ObjectiveTo comprehensively identify the O-methyltransferase （OMT） genes in Carthamus tinctorius and explore the key OMTs that can catalyze the methylation of flavonoids， providing a basis for understanding the molecular formation mechanism of the structural diversity of flavonoids in C. tinctorius. MethodsThe hidden Markov model was used to systematically identify the type Ⅰ OMTs from the high-quality genome data of C. tinctorius. A suite of bioinformatics tools was employed to systematically analyze the physicochemical properties， gene structure， conserved motifs， chromosomal localization， gene replication events， and collinearity of the identified genes. The target gene was heterologously expressed through the prokaryotic expression system of E. coli， and the protein function was verified by in vitro enzymatic reactions. ResultsA total of 31 type Ⅰ OMTs were identified. CtFOMT1 was successfully cloned and expressed in a soluble form in Escherichia coli. The recombinant protein was purified via Ni²⁺ affinity chromatography to obtain a high-concentration preparation. In vitro enzymatic assays demonstrated that CtFOMT1 utilized S-adenosylmethionine as the methyl donor to catalyze the methylation of the 4′-OH of naringenin， resulting in the production of isosakuranetin. A similar process occurred with the 4′-OH of luteolin， leading to the formation of diosmetin. Subsequent methylation of the 3′-OH group of diosmetin generated 4′-methylchrysoeriol. ConclusionCtFOMT1 can catalyze the methylation of 4′-/3′-OH in the flavonoid skeleton. It is hypothesized that CtFOMT1 may play a role in the biosynthesis of various 4′-/3′-oxymethyl flavonoids in C. tinctorius.

Conjunctival lymphangiectasia is a low-incidence ocular surface disease that is currently rarely reported in the relevant literature. It may be related to cosmetic eyelid surgery, tumor, radiation or chemotherapy and other factors and often causes a foreign body sensation, lacrimation, eye pain, visual fatigue and other discomfort. These symptoms of constant eye irritation affect the patient's quality of life. At present, anterior segment optical coherence tomography can be used for clinical diagnosis, and the novel monoclonal antibody D2-40, as a marker of lymphatic endothelial cell dilatation, has high specificity in pathological diagnosis. Previous studies have not fully defined the pathogenesis of the disease, and treatment methods vary. Conventional treatment has resulted in varying degrees of damage to the conjunctiva in patients. In recent years, anti-vascular endothelial growth factor drugs have been reported to be effective in treating the disease with few complications. This article reviews the pathogenesis, diagnosis and treatment of this rare disease in order to gain a better understanding of conjunctival lymphangiectasia and provide more support for clinical diagnosis and treatment.

Objective: To understand relationship of positive and negative peer events with mental health problems among college students, so as to provide a scientific basis for improving mental health level of college students. Methods: A total of 1 640 freshmen to juniors were randomly selected from two universities in Anhui Province from October to November 2023 by a combination of convenience sampling and cluster random sampling method. The positive and negative peer events, self perceived loneliness and stress levels, anxiety and depression symptoms of students were investigated by using the questionnaire star online. Group comparisons were conducted by using analysis of variance and Chi square test, and multivariate binary Logistic regression and linear regression were used to analyze relationship of positive and negative peer events with mental health problems among college students. Results: About 35.4% of college students reported that they experienced at least one type of negative peer events, and 91.3% reported that they experienced at least one type of positive peer events. After controlling for covariates,multivariate regression analysis found that experiencing 1, ≥2 types of negative peer events were positively correlated with loneliness scores of college students ( β = 1.36,4.04), as well as an increased risk of anxiety symptoms ( OR =2.24,4.33) and depression symptoms ( OR =2.19,4.01); and experiencing ≥2 types of negative peer events was positively correlated with stress scores of college students ( β =1.12)( P <0.05). Experiencing 5-6 and 7 types of positive peer events were negatively correlated with loneliness scores of college students ( β = -1.79, -2.44) and stress ( β =-0.75, -1.12); and experiencing 7 types of positive peer events were associated with a lower risk of anxiety symptoms ( OR =0.74) and depressive symptoms ( OR =0.80) ( P <0.05). The number of negative peer events was positively correlated with loneliness scores ( β =0.80) and stress scores( β =0.24), as well as the risk of anxiety symptoms ( OR =1.30) and depressive symptoms ( OR =1.27) among college students ( P <0.05). The number of positive peer events involved was negatively correlated with loneliness scores( β =-0.39) and stress scores( β =-0.19), as well as the risk of anxiety ( OR =0.92) and depressive symptoms ( OR =0.93) among college students ( P <0.05). The analysis of the moderating effect found that in different groups of positive peer events, reporting 1, ≥2 negative peer events were positively correlated with loneliness scores of college students ( β=1.08- 4.96), as well as an increased risk of anxiety symptoms ( OR =1.79-6.20) and depression symptoms ( OR =1.78-6.77) ( P <0.05); and β and OR coefficients were highest in the group reporting 0-4 types of positive peer events, followed by the group reporting 5-6 types of positive peer events, with lowest coefficients in the group reporting 7 types of positive peer events. Conclusions Negative peer events are positively correlated with psychological problems in college students, and positive peer events are negatively correlated with mental health problems. Positive peer events could alleviate the impact of negative peer events on mental health problems.

[Objective] To investigate the differences in metabolomics between apheresis platelets stored at 4℃ and at 22℃ with agitation, aiming to provide a theoretical basis for the cold storage of apheresis platelets. [Methods] Samples were collected at four time points (d1, d5, d10, d15) for platelets stored at 4℃ (experimental group) and two time points (d1, d5) for platelets stored at 22℃ with agitation (control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was used to detect changes in platelet metabolome levels under different storage conditions. Platelet functional activity was assessed by thromboelastography (TEG) for maximum amplitude (MA) values and flow cytometry for CD62P activation rates. [Results] Metabolites in the glycolytic pathway, key metabolites in the tricarboxylic acid cycle (citrate, α-ketoglutarate), metabolites in the purine metabolism pathway (adenine, inosine monophosphate, guanine, etc.) and amino acid metabolites significantly decreased by d5 in the control group, whereas they remained stable in the experimental group. The content of fatty acid metabolites, such as prostaglandin G2, 13(S)-HOTrE, and linoleic acid, significantly increased in the control group. Statistically significant differences in MA values were observed between the two groups at d1 and d5 (P<0.05). However, in the experimental group, as the storage time extended, the MA values at d10 and d15 showed no significant difference compared to the control group at d5 (P>0.05). The CD62P activation rate between the two groups was statistically significant (P<0.05). Additionally, the CD62P activation rate of platelets in the 22℃ group increased rapidly from d1, while it rose gradually in the 4 ℃ group. [Conclusion] Platelets stored at 4 ℃ exhibit more stable metabolic activity and slower functional deterioration, which is beneficial for extending the effective storage period of platelets.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To analyze the application efficacy of employing high-density porous polyethylene （Su-por） in combination with temporoparietal fascial flaps via a minimally invasive scalp incision in auricular reconstruction. Methods:This study carried out a retrospective analysis of 50 patients （50 ears in total） who underwentprimary auricular reconstruction with a Su-por scaffold in our hospital from June 2022 to January 2024. All patients underwent primary auricular reconstruction using a minimally invasive scalp incision with high-density porous polyethylene （Su-por） and temporoparietal fascial flaps. The postoperative treatment effects and complications were statistically analyzed. Results:The reconstructed ears of all patients survived. After 6 months of follow-up, the scar hyperplasia of the scalp minimally invasive incision was not obvious in any patient, and no significant hair loss was observed. The reconstructed auricle of 48 patients had a realistic shape and strong three-dimensional sense. With the extension of follow-up time, the three-dimensional structure of the auricle became clearer, and patient satisfaction increased. Among the remaining two patients, one case of flap necrosis survived after skin grafting and dressing changes. One patient had scar hyperplasia at the incision of the reconstructed ear due to a scar-prone constitution, and the shape of the auricle was not ideal, but the scar hyperplasia at the scalp incision was not obvious. Conclusion:One-stage ear reconstruction with high-density porous polyethylene （Su-por） combined with superficial temporal fascia flap through a minimally invasive scalp incision can better show the fine structure of the reconstructed ear. The minimally invasive scalp incision can effectively reduce the occurrence of scar hyperplasia and postoperative alopecia at the scalp incision.
Humans ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Surgical Flaps ; Tissue Scaffolds ; Polyethylene ; Ear Auricle/surgery* ; Male ; Scalp/surgery* ; Female ; Skin Transplantation ; Fascia/transplantation* ; Porosity ; Adult ; Middle Aged

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged