A bibliometric analysis of the research landscape on vascular normalization in cancer.

Tumor vascular normalization profoundly affects the advancement of cancer therapy. Currently, with the rapid increase in research on tumor vascular normalization, few analytical and descriptive studies have investigated the trends in its development, key research power, present research hotspots, and future outlooks. In this study, articles and reviews published between January 1, 2003, and October 29, 2022 were retrieved from Web of Science database. Subsequently, published research trends, countries/regions, institutions, authors, journals, references, and keywords were analyzed based on traditional bibliometric laws (such as Price's exponential growth, Bradford's, Lotka's, and Zipf's). Our results showed that the last two decades have seen an increase in tumor vascular normalization research. USA emerged as the preeminent contributor to the field, boasting the highest H-index and accruing the greatest quantity of publications and citations. Among institutions, Massachusetts General Hospital and Harvard University made significant contributions, and Professor RK Jain was identified as a key leader in this field. Out of 583 academic journals, Cancer Research and Clinical Cancer Research published the most articles on vascular normalization. The research focal points in the field primarily include immunotherapy, tumor microenvironments, nanomedicine, and emerging frontier themes such as metabolism and mechanomedicine. Concurrently, the challenges of vascular normalization in cancer are discussed as well. In conclusion, the study presented a thorough analysis of the literature covering the past 20 years on vascular normalization in cancer, highlighting leading countries, institutions, authors, journals, and the emerging research focal points in this field. Future studies will advance the ongoing efforts in the field of tumor vascular normalization, aiming to enhance our ability to effectively manage and treat cancer.

Evaluation of Secondary Alveolar Bone Grafting for Unilateral Complete Cleft Alveolus: A Retrospective Cone Beam Computed Tomography-Based Study.

Background: In patients with cleft lip and palate (CLP), secondary alveolar bone grafting (SABG) with particulate cancellous bone marrow (PCBM) is recommended. Objective: To compare bone graft outcomes in patients with unilateral CLP, when SABG is completed before or after canine tooth eruption (ACE or BCE), as measured by cone beam computed tomography (CBCT). Methods: Patients were allocated into two cohorts, ACE and BCE. The outcomes were evaluated using CBCT, followed by univariate and multifactorial analyses. Results: A total of 468 patients (age 11.61 ± 4.03 years; male/female 288/180) were analyzed, including 282 in the BCE group (9.41 ± 1.59 years, 175/107) and 186 in the ACE group (14.95 ± 4.31 years, 113/73). Although 5-level assessment revealed no significant difference in clinical success rate (>4 points) between the BCE and ACE groups (53.90% vs. 47.85%, p = 0.20), BCE group showed significantly higher rate of bone bridges formation (73.05% vs. 62.90%, p = 0.02), which can be attributed to variations in orthodontic participation and follow-up time. Independent predictors of graft failure were wide cleft, severe oronasal fistula, no palatal bone wall, and insufficient PCBM filling (p < 0.01). Conclusions: SABG should be performed before canine eruption with more aggressive PCBM filling and oral fistula management.

Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation.

Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

Predictive value of 18 F-FDG PET/CT versus bone marrow biopsy and aspiration in pediatric neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most prevalent solid extracranial malignancy in children, often with bone marrow metastases (BMM) are present. The conventional approach for detecting BMM is bone marrow biopsy and aspiration (BMBA). 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (18 F-FDG PET/CT) has become a staple for staging and is also capable of evaluating marrow infiltration. The consensus on the utility of 18 F-FDG PET/CT for assessing BMM in NB patients is still under deliberation. METHODS: This retrospective study enrolled 266 pediatric patients with pathologically proven NB. All patients had pretherapy FDG PET/CT. BMBA, clinical, radiological, and follow-up data were also collected. The diagnostic accuracy of BMBA and 18 F-FDG PET/CT was assessed. RESULTS: BMBAs identified BMM in 96 cases (36.1%), while 18 F-FDG PET/CT detected BMI in 106 cases (39.8%) within the cohort. The initial sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) of 18 F-FDG PET/CT were 93.8%, 84.9%, 90.6%, and 96.3%, respectively. After treatment, these values were 92.3%, 70.6%, 97.3%, and 99.4%, respectively. The kappa statistic, which measures agreement between BMBA and 18 F-FDG PET/CT, was 0.825 before treatment and 0.784 after treatment, with both values indicating a substantial agreement (P = 0.000). Additionally, the amplification of MYCN and a positive initial PET/CT scan were identified as independent prognostic factors for overall survival (OS). CONCLUSION: 18 F-FDG-PET/CT is a valuable method for evaluating BMM in NB. The routine practice of performing a BMBA without discrimination may need to be reassessed. Negative result from 18 F-FDG-PET/CT could potentially spare children with invasive bone marrow biopsies.

Synergistic Strain Suppressing and Interface Engineering in Na4MnV(PO4)3/C for Wide-Temperature and Long-Calendar-Life Sodium-Ion Storage.

A Na4MnV(PO4)3 (NMVP) cathode is regarded as a promising cathode candidate for sodium-ion batteries (SIBs). However, issues such as low electronic conductivity and partial cation dissolution contribute to high polarization and structure distortion. Herein, we engineered the local electron density and reaction kinetic properties of NMVP cathodes with varying oxygen vacancies by introducing varying amounts of Zr doping and carbon coating. The optimized sample exhibited a high-rate capacity of 71.8 mAh g-1 at 30 C (83.1% capacity retention after 1000 cycles) and excellent performance over a wide temperature range (84.1 mAh g-1 at 60 °C and 61.4 mAh g-1 at -30 °C). In situ X-ray diffraction technology confirmed a redox solid solution and a two-phase reaction mechanism, revealing minor changes in cell volume and slight strain variations after Zr doping, effectively suppressing the structural distortion. Theoretical calculations illustrated that Zr doping largely shrinks the band gap of NMVP, enriches local electron density, and slightly alters the local element distribution and bond lengths. Moreover, full-cells have shown high energy density (259.9 Wh kg-1) and outstanding cycling stability (200 cycles). The work provides fresh insights into the synergistic effect of strain suppressing and interface engineering in promoting the development of wide temperature range and long-calendar-life SIBs.

Impact of organic matter molecular weight on hexavalent chromium enrichment in green microalgae.

In lightly polluted water containing heavy metals, organic matter, and green microalgae, the molecular weight of organic matter may influence both the growth of green microalgae and the concentration of heavy metals. This study elucidates the effects and mechanisms by which different molecular weight fractions of fulvic acid (FA), a model dissolved organic matter component, facilitate the bioaccumulation of hexavalent chromium (Cr(VI)) in a typical green alga, Chlorella vulgaris. Findings show that the addition of FA fractions with molecular weights greater than 10 kDa significantly enhances the enrichment of total chromium and Cr(VI) in algal cells, reaching 21.58%-31.09 % and 16.17 %-22.63 %, respectively. Conversely, the efficiency of chromium enrichment in algal cells was found to decrease with decreasing molecular weight of FA. FA molecular weight within the range of 0.22 µm-30 kDa facilitated chromium enrichment primarily through the algal organic matter (AOM) pathway, with minor contributions from the algal cell proliferation and extracellular polymeric substances (EPS) pathways. However, with decreasing FA molecular weight, the AOM and EPS pathways become less prominent, whereas the algal cell proliferation pathway becomes dominant. These findings provide new insights into the mechanism of chromium enrichment in green algae enhanced by medium molecular weight FA.

Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis.

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; Epub ahead of print.

Photoinduced decatungstate-catalyzed C(sp3)-H thioetherification by sulfinate salts.

Thiols and thioesters play crucial roles in pharmaceuticals, biology, and material science as essential organosulfur compounds. Leveraging readily available and cost-effective inert alkanes through direct thioetherification holds promise for yielding high-value-added products. Herein, we present a photoinduced strategy for sulfur-containing modification of inert alkanes utilizing decatungstate as hydrogen atom transfer reagent, offering a straightforward and practical approach for synthesizing thioethers and thioesters.

Associations between heat waves and chronic kidney disease in China: The modifying role of land cover.

The increasing frequency of heat waves under the global urbanization and climate change background poses elevating risks of chronic kidney disease (CKD). Nevertheless, there has been no evidence on associations between long-term exposures to heat waves and CKD as well as the modifying effects of land cover patterns. Based on a national representative population-based survey on CKD covering 47,086 adults and high spatial resolution datasets on temperature and land cover data, we found that annual days of exposure to heat waves were associated with increased odds of CKD prevalence. For one day/year increases in HW_975_4d (above 97.5 % of annual maximum temperature and lasting for at least 4 consecutive days), the odds ratio (OR) of CKD was 1.14 (95 %CI: 1.12, 1.15). Meanwhile, stronger associations were observed in regions with lower urbanicity [rural: 1.14 (95 %CI: 1.12, 1.16) vs urban: 1.07 (95 %CI: 1.03, 1.11), Pinteraction < 0.001], lower water body coverage [lower: 1.14 (95 %CI: 1.12, 1.16) vs higher: 1.02 (95 %CI: 0.98, 1.05), Pinteraction < 0.001], and lower impervious area coverage [lower: 1.16 (95 %CI: 1.14, 1.18) vs higher: 1.06 (95 %CI: 1.03, 1.10), Pinteraction = 0.008]. In addition, this study found disparities in modifying effects of water bodies and impervious areas in rural and urban settings. In rural regions, the associations between heat waves and CKD prevalence showed a consistent decreasing trend with increases in both proportions of water bodies and impervious areas (Pinteraction < 0.05). Nevertheless, in urban regions, we observed significant effect modification by water bodies, but not by impervious areas. Our study indicates the need for targeted land planning as part of adapting to the kidney impacts of heat waves, with a focus on urbanization in rural regions, as well as water body construction and utilization in both rural and urban regions.

Incidence, prevalence, and medical costs of pressure injuries in Taiwan from 2001 to 2015: Results of a retrospective cohort study.

AIMS AND OBJECTIVES: This study aims to analyse the trends in the incidence, prevalence and medical costs of pressure injuries (PIs) among genders in Taiwan. BACKGROUND: The treatment of PIs is complex and costly, often leading to complications and increased mortality. This issue significantly impacts healthcare quality and incurs substantial medical and social costs, warranting attention. METHODS: A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Database to obtain and calculate the incidence, prevalence, and medical costs of PIs in the country between 2001 and 2015 as well as to analyse high-risk groups and the medical care utilisation of patients following the STROBE reporting guidelines. RESULTS: Between 2001 and 2015, 15,327 incident case of PIs were diagnosed. During the study period, the prevalence rate of PIs per 100,000 population rose from 26.3 to 189.6, with approximately 11.5%-16.3% of patients undergoing surgical debridement. The PIs prevalence rate increased by 7.2-fold, and hospitalisation costs accounted for 91.7%-96.0% of the total medical costs. Patients with older age, comorbidities, poorer financial status and lower education levels were found to be likely to develop PIs. These predisposing factors differed between males and females. The prevalence of PIs was higher in patients ≥75 years old than in patients from other age groups. Moreover, PI-related medical expenses have been increasing annually. CONCLUSIONS: In Taiwan, the rising incidence of PIs is driving up medical costs. Effective care and prevention of PIs necessitate a comprehensive plan from the entire healthcare system. RELEVANCE TO CLINICAL PRACTICE: This research fills a gap in the available data on the incidence, prevalence, and medical costs of PIs in Taiwan and Asia. PATIENT OR PUBLIC CONTRIBUTION: The findings can be used to help develop clinical guidelines for preventive education and treatment of PIs.

Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.

Spatiotemporal distribution of mediastinal neoplasms: A comprehensive multi-center study.

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.

Monolithic Interphase Enables Fast Kinetics for High-Performance Sodium-Ion Batteries at Subzero Temperature.

In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5 M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8% after 900 cycles at 1 C, a capacity over 310 mA h·g-1 under -30 ºC, respectively, showing long-term cycling stability and great rate capability at low temperature.

FOXO3 Inhibits the Cisplatin Resistance and Progression of Melanoma Cells by Promoting CDKN1C Transcription.

BACKGROUND: Forkhead box O3 (FOXO3) and cyclin dependent kinase inhibitor 1 C Gene (CDKN1C) have been shown to be involved in the melanoma process, but their roles in the cisplatin (DDP) resistance of melanoma remain unclear. METHODS: The mRNA levels of CDKN1C and FOXO3 were measured using quantitative real-time PCR. The protein levels of CDKN1C, FOXO3 and mitochondrial oxidative phosphorylation (mtOXPHOS)-related markers were determinant by western blot analysis. The DDP resistance, proliferation, and apoptosis of melanoma cells were assessed by cell counting kit 8 assay, colony formation assay and flow cytometry. Glucose consumption, lactate production and ATP level were detected to assess glycolysis. The regulation of FOXO3 on CDKN1C was confirmed by ChIP assay and dual-luciferase reporter assay. In vivo experiments were performed to evaluate the effect of FOXO3 on DDP sensitivity in melanoma tumor tissues. RESULTS: CDKN1C and FOXO3 were downregulated in chemoresistant melanoma tissues, and their low expression levels were related to the poor prognosis of melanoma patients. Overexpression of CDKN1C and FOXO3 repressed DDP resistance, proliferation, and glycolysis, while promoted apoptosis and mtOXPHOS in DDP-resistant melanoma cells. Further analysis suggested that FOXO3 could bind to CDKN1C promoter region to enhance its transcription. Besides, CDKN1C knockdown reversed the regulation of FOXO3 on melanoma cell DDP resistance and progression. Moreover, FOXO3 overexpression enhanced the DDP sensitivity of melanoma tumor tissues in vivo. CONCLUSION: FOXO3 promoted the transcription of CDKN1C, thereby inhibiting the DDP resistance and progression of melanoma cells.

Treatment of metastatic TFE3 microphthalmia transcription factor translocation renal cell carcinoma: a case report.

Background: Microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) translocation renal cell carcinoma (RCC) is a rare type of non-clear cell RCC (nccRCC), which is more common in females. Currently, there is no standardized treatment for advanced metastatic microphthalmia translocation RCC (MiT-RCC). The main treatment modalities include surgery, chemotherapy, immunotherapy, anti-vascular endothelial growth factor or vascular endothelial growth factor receptor (VEGFR) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and targeted therapy against the mesenchymal-epithelial transition (MET) factor signaling pathway. Case Description: We present the case of an 8-year-old male patient with hematuria and paroxysmal urinary pain. Based on tumor genetic testing results and targeted drug matching analysis, the patient underwent tumor biopsy, tumor radical surgery with vascular osteotomy, and cervicothoracic lymph node dissection. The patient was then treated with a combination of immunotherapy [sintilimab, a drug directed against programmed cell death receptor-1 (PD-1)] and VEGFR tyrosine kinase inhibitor (TKI) (from pazopanib to sunitinib). Throughout the 10 cycles of conventional chemotherapy (seven courses of sintilimab since the start of the third chemotherapy treatment), the patient's condition remained stable, with no tumor recurrence at the primary site. However, in the later stages, the patient developed a large amount of ascites, and the family requested discontinuation of treatment, ultimately leading to the patient's death. Conclusions: In this case report, we summarize the therapeutic strategy of a young patient with metastatic transcription factor E3 (TFE3) MiT-RCC. For this disease, early immunotherapy and the use of precision-targeted drugs may have a favorable impact on the survival prognosis of the patient but may still be of less benefit in children with advanced multiple metastases. Therefore, further research on tumor driver genes, among other treatment components, is urgently needed to improve precision therapy.

Genetically predicted causal effects of gut microbiota on spinal pain: a two-sample Mendelian randomization analysis.

Background: Observational studies have hinted at a correlation between the gut microbiota and spinal pain (SP). However, the impact of the gut microbiota on SP remains inconclusive. Methods: In this study, we employed a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between the gut microbiota and SP, encompassing neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). The compiled gut microbiota data originated from a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 18,340). Summary data for NP were sourced from the UK Biobank, TSP from the FinnGen Biobank, and LBP from both the UK Biobank and FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. The primary analytical approach for assessing causal relationships was the Inverse Variance Weighted (IVW) method, supplemented by various sensitivity analyses to ensure result robustness. Results: The IVW analysis unveiled 37 bacterial genera with a potential causal relationship to SP. After Benjamini-Hochberg corrected test, four bacterial genera emerged with a strong causal relationship to SP. Specifically, Oxalobacter (OR: 1.143, 95% CI 1.061-1.232, P = 0.0004) and Tyzzerella 3 (OR: 1.145, 95% CI 1.059-1.238, P = 0.0007) were identified as risk factors for LBP, while Ruminococcaceae UCG011 (OR: 0.859, 95% CI 0.791-0.932, P = 0.0003) was marked as a protective factor for LBP, and Olsenella (OR: 0.893, 95% CI 0.839-0.951, P = 0.0004) was recognized as a protective factor for low back pain or/and sciatica. No significant heterogeneity or horizontal pleiotropy was observed through alternative testing methods. Conclusion: This study establishes a causal relationship between the gut microbiota and SP, shedding light on the "gut-spine" axis. These findings offer novel perspectives for understanding the etiology of SP and provide a theoretical foundation for potential interventions targeting the gut microbiota to prevent and treat SP.

Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module.

Plants undergo various age-dependent changes in leaf morphology during the transition from the juvenile to the adult stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a-MdSPL14-MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a-MdSPL14-MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.

Exercise, weight maintenance, and nonalcoholic fatty liver disease risk: a Chinese cohort study.

Background: Exercise has been reported to be associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD), but there is no consensus on the role of weight changes in this association. This study aims to investigate whether the impact of exercise on NAFLD is mainly dependent on weight changes or is inherent to exercise itself. Methods: The study recruited 1671 Chinese NAFLD-free adults in 2019, and collected their exercise habits as well as 3 years of medical examination data including anthropometric measurements, blood biochemistry parameters, and liver ultrasound results. Univariate and multivariate logistic regression models were employed to examine the impact of exercise habits on NAFLD risk, with mediation analysis utilized to estimate the magnitude of the role of weight maintenance in the association between exercise and NAFLD. Results: After adjusting for confounders, moderate to high-intensity exercisers were 1.56 times (95% CIs = 1.09-2.22) more likely to successfully control their body weight, and therefore the weight-controlled group had a lower NAFLD risk of 34.9% (95% CIs = 21.8%-56.0%) compared to the weight-gain group. Mediation analysis reveals that exercise can significantly reduce the risk of NAFLD both through weight maintenance (37.1%) and independent of weight maintenance (62.9%). Conclusion: It might be more crucial to emphasize the adoption of regular moderate to high-intensity exercise for preventing NAFLD in the general population, rather than solely focusing on weight maintenance.

Development of an Imidazopyridazine-Based MNK1/2 Inhibitor for the Treatment of Lymphoma.

The mitogen-activated protein kinase-interacting protein kinases (MNKs) are the only kinases known to phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at Ser209, which plays a significant role in cap-dependent translation. Dysregulation of the MNK/eIF4E axis has been found in various solid tumors and hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). Herein, structure-activity relationship studies and docking models determined that 20j exhibits excellent MNK1/2 inhibitory activity, stability, and hERG safety. 20j exhibits strong and broad antiproliferative activity against different cancer cell lines, especially GCB-DLBCL DOHH2. 20j suppresses the phosphorylation of eIF4E in Hela cells (IC50 = 90.5 nM) and downregulates the phosphorylation of eIF4E and 4E-BP1 in A549 cells. In vivo studies first revealed that ibrutinib enhances the antitumor effect of 20j without side effects in a DOHH2 xenograft model. This study provided a solid foundation for the future development of a MNK inhibitor for GCB-DLBCL treatment.

Heparin-free veno-arterial extracorporeal membrane oxygenation in lung transplantation: a retrospective cohort study.

BACKGROUND: In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies. METHODS: From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group. RESULT: There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095). CONCLUSIONS: In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.