Structurally diverse triterpenoid alkaloids from Buxus rugulosa.

Four new nortriterpenoid alkaloids, namely buxrugulines E-H (1-4), along with five known ones (5-9), were isolated from the twigs and leaves of Buxus rugulosa. Their structures were identified based on extensive NMR data and MS spectroscopic analyses. Our bioassays revealed that compounds 5, 6 and 8 exhibited potent cytotoxicity in vitro against MCF-7 cell lines, with IC50 values ranging from 6.70 to 11.00 µM, respectively.

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

Impact of dietary sucralose and sucrose-sweetened water intake on lipid and glucose metabolism in male mice.

AIMS: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. MATERIALS AND METHODS: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. RESULTS: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. CONCLUSION: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.

'Chinese academia wouldn't be tolerant of my research': gay academics' concerns about conducting queer research in China.

Drawing on interviews with 40 Chinese gay academics, this paper reveals participants' concerns about conducting queer research in China. These include sexual-identity exposure, difficulty in publishing research and receiving funding, as well as marginalisation within university departments. Informed by Irvine's conceptualisation of sexuality research as dirty work, this research examines the operation of heteronormativity in the constitution of queer research as dirty work. It shows that heteronormativity is intrinsic to research censorship by authorities, as repressive politics pursue regime maintenance and regulate difference. It is argued that Chinese academia is a heteronormative space in which queer research is constrained by the institutions and the Party-state. By teasing out the nuances in participants' experiences of research censorship, this paper highlights the complexity of power at play, which is far from a one-way relationship of authorities exerting power over researchers. Institutions exert power over queer researchers and simultaneously submit to the higher-level power of the Chinese Communist Party political system; at the same time, queer researchers who are governed by heteronormativity and political control can express their agency and resist the censorship.

Phagocytosis-Regulators-Based Signature to Predict the Prognosis and Chemotherapy Resistance for Breast Cancer Patients.

Phagocytosis is crucial in tumor surveillance and immune function. The association between phagocytosis and the outcomes of breast cancer patients has not been well-determined. In this study, data were downloaded from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases to investigate the role of phagocytosis in breast cancer. Data from the TCGA and GEO databases were used to investigate the prognostic role of phagocytosis in breast cancer. Then, we performed pathway enrichment analysis, copy number variation (CNV) and single-nucleotide variant (SNV) analyses, immune infiltration analysis, calculation of tumor purity, stromal score, and immune score, and consistent clustering. We also constructed a phagocytosis-regulators-based signature system to examine its association in survival and drug response. The genomic and expression differences in the phagocytosis regulators in breast cancer were systematically analyzed, explaining the widespread dysregulation of phagocytosis regulators. Using the investigated association of phagocytosis regulators with the prognosis and tumor immune environment, we constructed a prognostic model based on phagocytosis regulators. We discovered that patients with high risk scores had a poor prognosis and were negatively associated with immune functions. The model had preferential predictive performance and significantly consistent drug-resistance prediction results. Our findings suggest that the phagocytosis-factors-based scoring system can be used as a novel prognostic factor, serving as a powerful reference tool for predicting prognosis and developing methods against drug resistance.

Metabolic gene signature for predicting breast cancer recurrence using transcriptome analysis.

Background: The study aimed at identifying a metabolic gene signature for stratifying the risk of recurrence in breast cancer. Materials & methods: The data of patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The limma package was used to identify differentially expressed metabolic genes, and a metabolic gene signature was constructed. Results: A five-gene metabolic signature was established that demonstrated satisfactory accuracy and predictive power in both training and validation cohorts. Also, a nomogram for predicting recurrence-free survival was established using a combination of the metabolism gene risk score and the clinicopathological features. Conclusions: The proposed metabolic gene signature and nomogram have a significant prognostic value and may improve the recurrence risk stratification for breast cancer patients.

Levels of nasal exhaled hydrogen sulfide in the general population and allergic rhinitis patients.

BACKGROUND: Objective measures used for the differential diagnosis and severity assessment of allergic rhinitis (AR) are still lacking. The involvement of hydrogen sulfide (H2 S) in the development of AR indicates that nasal exhaled H2 S (NeH2 S) has potential as a biomarker to be used in AR patients. This study aimed to evaluate the application value of NeH2 S measurement in the diagnosis and assessment of AR. METHODS: This study was a multi-center cross-sectional survey conducted in Northwestern China. Demographic information collection and rhinitis assessment were completed through questionnaires. The level of NeH2 S and serum immunoglobulin E were measured. RESULTS: The level of NeH2 S in general population ranged from 0 to 35 ppb, with a median value of 2 ppb. The NeH2 S levels in seasonal allergic rhinitis (SAR) patients were significantly lower than those in general population (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .023), and the NeH2 S value of the SAR group tended to be lower than that of the non-allergic rhinitis (NAR) group (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .094). The subgroup of AR patients with symptoms lasting longer than 2 weeks per month had a lower NeH2 S level compared with the subgroup of patients with symptoms lasting less than 2 weeks per month (2 [1, 2] vs. 2 [2, 3] ppb; p = .015). CONCLUSION: This study described the distribution range of NeH2 S levels in the general population. Further study with larger sample size was needed to clarify the relationship between NeH2 S level and AR.

[Changes and Related Reflections on the European Union's in Vitro Diagnostic Medical Device Classification Supervision System].

By analyzing and comparing the IVD product classification supervision system in the EU's new IVDR, old IVDD and related guidance documents, concepts of related regulatory reforms were analyzed and explored, to provide references for industrial personnel to understand and master the new EU IVD classification system, and for China's ongoing classification management reform.

Association of serum specific IgE levels with asthma in autumn pollen-induced allergic rhinitis: A retrospective analysis.

BACKGROUND: Artemisia and Humulus pollen are the two most important aeroallergens of autumn allergies in North China. Cross-sectional data in 2001 have shown that allergic rhinitis often preceded or occurred at the same time as asthma in patients with autumn pollinosis in North China. OBJECTIVE: We used this cross-sectional data to investigate the association of serum specific IgE (sIgE) levels to Humulus and/or Artemisia pollen with the onset of asthma in patients with autumn pollen-induced allergic rhinitis. METHODS: 1096 patients with autumn pollinosis were face-to-face interviewed and underwent sIgE tests to Artemisia and Humulus. The temporal sequence of allergic rhinitis and asthma was documented. 1013 patients were positive to Artemisia and/or Humulus by sIgE. Multinomial logistic regression and survival analysis were used to examine the potential implication of sIgE levels for the progression of asthma in autumn pollen-induced allergic rhinitis. RESULTS: Of the 1013 participants with a positive sIgE test to Artemisia and/or Humulus, 563 (55.6%) had a history of allergic rhinitis which preceded or occurred at the same time as asthma. 450 (44.4%) had allergic rhinitis alone. After controlling of sex, age at onset of allergic rhinitis, and parental asthma, the risk of developing asthma increased with the levels of sIgE to both Artemisia and Humulus (p < 0.05). In Kaplan-Meier analysis, IgE classes 5-6 to Humulus or Artemisia increased the risk of asthma development (p < 0.05). CONCLUSION: Autumn pollen-induced allergic rhinitis often coexists with seasonal asthma. The incidence of asthma is more pronounced when the sIgE level was higher.

Variability of macroscopic dimensions of Moso bamboo.

In order to the macroscopic geometry distributions of vascular bundles in Moso bamboo tubes. The circumference of bamboo tubes was measured, used a simple quadratic diameter formula to analyze the differences between the tubes in bamboo culm, and the arrangement of vascular bundles was investigated by cross sectional images of bamboo tubes. The results shown that the vascular bundles were differently distributed in a bamboo tube. In the outer layer, the vascular bundles had a variety of shapes, and were aligned parallel to each other. In the inner layers, the vascular bundles weren't aligned but uniform in shape. It was concluded that the vascular bundle sections arranged in parallel should be separated from the non-parallel sections for the maximum bamboo utilization.

Granulomatous mastitis in a 50-year-old male: A case report and review of literature.

BACKGROUND: Granulomatous mastitis (GM) an inflammatory disease of the breast that usually affects women of childbearing age, occurs very rarely in males. CASE SUMMARY: We present a case study of a 50-year-old male patient with GM. The patient developed a breast lump following the cleaning of a previously embedded dirt-filled nipple. While an initial improvement was noted with antibiotic therapy, a recurrence occurred a year later, showing resistance to the previously effective antibiotics. Subsequently, the lesion was excised. The histopathological examination confirmed the diagnosis of GM. CONCLUSION: GM should be considered a possible diagnosis of male breast masses.

METTL1-mediated tRNA m7G methylation and translational dysfunction restricts breast cancer tumorigenesis by fueling cell cycle blockade.

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.

Clinical profiles of patients with wheat-induced anaphylaxis at various ages of onset.

Background: Wheat-induced anaphylaxis (WIA) is a serious and potentially life-threatening wheat allergy, more common in adults than in children. Little is known about the differences in clinical profiles in WIA among patients of various ages in China. Methods: We analyzed data retrospectively from an allergy department in a tertiary hospital that included 248 patients (208 adults and 40 children and adolescents) with a history of WIA. Results: We found that alcohol was more frequent in patients aged ≥50 years [older adults] (19.0%, 4/21) than in those aged 12-17 years [adolescents] (0%, 0/33; p = 0.019). The frequency of NSAID use in older adults (42.9%, 9/21) was significantly higher than that in adolescents (0%, 0/33; p < 0.001), and patients aged 18-49 years [young adults] (2.8%, 5/178; p < 0.001). During WIA, cardiovascular symptoms in children were less frequent than those in other age groups (children, 28.6%; adolescents, 87.9%; young adults, 93.0%; older adults, 95.2%; p < 0.001). The consciousness loss rate in adults (both age groups; p < 0.001) and the hypotension rate in older adults (p = 0.006) were higher than those in other age groups. Compared with adults (young and older adults), children had a higher rate of allergic comorbidities (p = 0.004, 0.001, respectively) and a higher rate of other food allergies (p < 0.001, <0.001, respectively). Compared with the mild-to-moderate anaphylaxis group, the severe anaphylaxis group had a higher onset age (p = 0.001), higher cofactor prevalence (p = 0.004), lower allergic comorbidity rate (p = 0.014), and higher positive rate of specific IgE to omega-5 gliadin (ω-5 gliadin) (p = 0.023). Conclusion: Clinical profiles of patients with WIA are different among various onset age/severity groups. An improved understanding of WIA symptoms in various age/severity groups could help accelerate diagnosis, suggest preventive measures, and contribute to improved patient care.

The efficacy of a novel smart watch on medicine adherence and symptom control of allergic rhinitis patients: Pilot study.

Background: Allergic rhinitis (AR) is a common allergic airway disorder that is often poorly managed. There is an urgent need to enhance medication adherence in order to improve treatment outcomes in patients with AR. The efficacy of wearable smart watches in improving medication adherence is currently unclear. Objectives: This study aimed to evaluate the efficacy of a novel smart watch in improving medication adherence and symptom control in patients with AR. The reliability of self-reported medication use was also investigated. Methods: This randomized, open-label, parallel controlled, pilot study enrolled adult patients with AR caused by cypress pollen. Patients were randomized in a 1:2 ratio to an intervention group and control group. Smart watches were only distributed to patients in the intervention group. During the cypress pollen season, all patients were required to take oral antihistamines daily and use nasal corticosteroids and antihistamine eye drops as needed. Daily AR symptom scores and medication usage were recorded in both groups. The smart watch was able to identify medication-taking behaviors of patients via artificial intelligence (AI) and relay this information to physicians, who sent short message service reminders to patients who forgot to take oral antihistamines for more than 2 days. Results: During the pollen season, the adherence rate to oral antihistamines in the intervention group (n = 17) was significantly higher than that in the control group (n = 38) (63.3% ± 28.5% versus 43.2% ± 30.2%, P = 0.02). The daily symptom score of the intervention group was lower than that of the control group (2.4 ± 1.1 versus 3.9 ± 1.0, P < 0.001). There was no significant difference in the on-demand medication score between the 2 groups (1.3 ± 0.4 versus 1.5 ± 0.5, P = 0.13). The consistency rate between self-reported nasal corticosteroid usage and the gold standard (ie, human observation of medication usage in the videos recorded by the smart watch) was 20.0% (0%, 53.7%), and the consistency rate between self-reported antihistamine eye drop usage and the gold standard was 24.3% (2.1%, 67.1%). Conclusions: This pilot study showed that the application of smart watches in patients with AR was associated with improved medication adherence and symptom control. Furthermore, the reliability of self-reported medication usage was limited.

Association between iodine nutrition and cervical lymph node metastasis of papillary thyroid microcarcinoma.

We aimed to investigate the association between iodine intake and nodal metastasis stratified by central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) of papillary thyroid microcarcinoma (PTMC). Urinary iodine concentration (UIC) and clinicopathological characteristics were used to identify factors associated with CLNM and LLNM using logistic regression analysis. A sum of 3,858 PTMC patients were enrolled. The median UIC (MUI) of patients with CLNM or LLNM was not statistically different from those without nodal metastasis. Male patients had a higher MUI than females (183.4 µg/L vs. 173.6 µg/L). Female patients with extracapsular extension had a higher MUI than those without it (210.0 µg/L vs. 172.1 µg/L). Male patients with LLNM had a significantly lower MUI than those without LLNM (134.7 µg/L vs. 187.9 µg/L). Female patients with more than adequate iodine intake were more likely to present with CLNM and extrathyroidal extension than those with adequate iodine intake with an odds ratio (95% confidence interval) of 1.23 (1.01-1.51) and 1.59 (1.09-2.32) after adjustment. Iodine nutrition was not found to be associated with LLNM. In addition, patients with a younger age, larger tumors, extrathyroidal extension, and intrathyroidal spread were more likely to be CLNM, whereas nodular goiter presented with a protective factor; CLNM was the only factor associated with LLNM of PTMC in both genders. In conclusion, iodine nutrition has a much closer association with female than male patients, and high iodine intake may be associated with CLNM and extrathyroidal extension in female PTMC patients.

A new amide from the marine sponge Haliclona baeri.

A new amide, baeriamide (1), along with nine known diketopiperazines (2-10), was isolated from the marine sponge Haliclona baeri. Their structures were identified by the means of UV, IR, MS and NMR. The absolute configuration of 1 was established by Marfey's method and comparing the specific optical rotation with the known compound HCO-Val-Gly methyl ester. Compound 1 was derived from dehydration of formylated L-valine with γ-amino-butanoic acid methyl ester. Compounds 2-10 were isolated from the genus of Haliclona for the first time. The absolute confirmation of 7 was confirmed first by the means of single-crystal X-ray diffraction. The cytotoxic, antibacterial, antiviral and antifouling activities of these compounds were also tested. However, none of them exhibited significant bioactivities.

Combinations of Scheimpflug tomography, ocular coherence tomography and air-puff tonometry improve the detection of keratoconus.

PURPOSE: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.

Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice.

During cold exposure, activated brown adipose tissue (BAT) takes up a large amount of circulating glucose to fuel non-shivering thermogenesis and defend against hypothermia. However, little is known about the endocrine function of BAT controlling glucose homoeostasis under this thermoregulatory challenge. Here, we show that in male mice, activated BAT-derived extracellular vesicles (BDEVs) reprogram systemic glucose metabolism by promoting hepatic gluconeogenesis during cold stress. Cold exposure facilitates the selective packaging of miR-378a-3p-one of the BAT-enriched miRNAs-into EVs and delivery into the liver. BAT-derived miR-378a-3p enhances gluconeogenesis by targeting p110α. miR-378 KO mice display reduced hepatic gluconeogenesis during cold exposure, while restoration of miR-378a-3p in iBAT induces the expression of gluconeogenic genes in the liver. These findings provide a mechanistic understanding of BDEV-miRNA as stress-induced batokine to coordinate systemic glucose homoeostasis. This miR-378a-3p-mediated interorgan communication highlights a novel endocrine function of BAT in preventing hypoglycemia during cold stress.

Effect of fluence levels on prophylactic corneal cross-linking for laser in situ keratomileusis and transepithelial photorefractive keratectomy.

PURPOSE: The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze. METHODS: Prospective analysis where two prophylactic CXL protocols (lower/higher fluence [LF/HF]: 30 mw/cm2 , 60/80 s, 1.8/2.4 J/cm2 ) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm. RESULTS: Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6 months postoperatively (p = 0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1 month postoperatively, there was no statistical difference in mean ADL among four groups (p = 0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group. CONCLUSIONS: FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed.

New keratoconus staging system based on OCT.

PURPOSE: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGNS: Retrospective case-control study. METHODS: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. RESULTS: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. CONCLUSIONS: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.