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Objective: Previous studies showed an inconsistent association of fruit and vegetable consumption with bone health. We assessed the associations in Chinese adolescents, young and postmenopausal women.Design: A cross-sectional study conducted in China during July 2009 to May 2010.Setting: Bone mineral density (BMD) and content (BMC) at the whole body, lumbar spine and left hip were measured with dual-energy X-ray absorptiometry. Dietary intakes were assessed using an FFQ. All these values were separately standardized into Z-scores in each population subgroup.Subjects: One hundred and ten boys and 112 girls (11-14 years), 371 young women (20-34 years, postpartum within 2 weeks) and 333 postmenopausal women (50-70 years).Results: After adjustment for potential covariates, analysis of covariance showed a significantly positive association between fruit intake and BMD and BMC in all participants combined (P-trend: < 0.001 to 0.002). BMD Z-score increased by 0.25 (or 2.1 % of the mean), 0.22 (3.5 %), 0.23 (3.0 %) and 0.25 (3.5 %), and BMC Z-score increased by 0.33 (5.7 %), 0.25 (5.8 %), 0.34 (5.9 %) and 0.29 (4.7 %), at the total body, lumbar spine, total hip and femoral neck in participants belonging to the top tertile compared with the bottom tertile of fruit intake (all P < 0.05), respectively. There was no significant association between vegetable intake and bone mass at all bone sites studied except for total body BMD (P = 0.030). Relatively more pronounced effects were observed in boys and postmenopausal women.Conclusion: Our findings add to the existing evidence that fruits and vegetables may have a bone sparing effect. [ABSTRACT FROM AUTHOR]

We summarize the mechanism by which taurine (Tau) inhibits autophagy and induces iron apoptosis in hepatic stellate cells. Tau interacts with autophagy regulates multifunctional proteins, microtubule-associated protein 1 light chain 3 Beta, and autophagy-related gene 5 to inhibit autophagy, binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy, and interacts with glutathione peroxidase 4 to promote iron apoptosis. There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation. From a pharmaceutical point of view, there are certain requirements for Tau protein delivery systems, such as loading efficiency, stability, and targeting. Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency. Since Tau is a hydrophilic molecule with high water solubility, liposomes, micelles, and amphiphilic polymer nanoparticles may represent a superior choice. The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs, respectively, whereas Tau is expected to be loaded into the water region. In addition, a representative method of actively targeting hematopoietic stem cells is introduced. A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes (lecithin plus cholesterol)., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The purpose of this study is to explore the glycolytic remodeling under high-selenium (Se) stress. Three groups of male C57BL/6J mice were fed on diets with different Se contents (0.03, 0.15, and 0.30 mg Se/kg). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were measured at the third month. Mice were killed at the fourth month. Plasma, liver, and muscle tissues were fetched for biochemistry and Se analysis. The expressions of insulin signaling pathway (PI3K-AKT-mTOR), glutathione peroxidase 1 (GPX1), selenoprotein N (SELENON), 3-phosphoglycerate dehydrogenase (PHGDH), serine hydroxymethyltransferases 1 (SHMT1), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MS) were analyzed by western blotting (WB) in liver and muscle tissues. The results of GTT and ITT showed that glucose tolerance and insulin tolerance were both abnormal in the 0.03 mg Se/kg and 0.3 mg Se/kg groups. Se concentrations in plasma, liver, and muscle of 0.03 mg Se/kg group were significantly lower than that of 0.15 mg Se/kg and 0.30 mg Se/kg groups (p < 0.05 or p < 0.01). The expressions of P-Akt (Thr-308) in muscle (p < 0.05) and PI3K and mTOR in liver (p < 0.001) of 0.30 mg Se/kg group were downregulated. The expressions of GPX1 in liver and muscle (p < 0.05 and p < 0.001), SELENON in muscle (p < 0.05), PHGDH in liver and muscle (p < 0.05), and SHMT1 (p < 0.05), MTHFR (p < 0.001), and MS (p < 0.001) in muscle of 0.3 mg Se/kg group were upregulated. The de novo serine synthesis pathway (SSP) was found to be activated in liver and muscle tissues of mice with a high-Se diet for the first time., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We aimed to investigate the potential correlation between the placement factors of various retrievable inferior vena cava filters and retrieval outcomes. Additionally, we aimed to identify the factors affecting the placement tilt of the filter., Methods: This retrospective study was conducted at a tertiary care center to investigate patients who had previously undergone retrievable filter placement at our center and who subsequently had their filters removed between January 2020 and December 2021. Patient characteristics and filter-related factors were recorded. Complex filter retrieval was defined as cases that required a minimum of 8 minutes of fluoroscopy or that involved advanced techniques. Regression models were used to explore patient- and placement procedure-related factors that could influence retrieval outcomes and the placement tilt angle., Results: The study included 163 patients, and all filters were successfully retrieved. Thirty-seven (22.7%) retrievals were classified as complex retrievals. The mean diameter of the inferior vena cava in the preplacement position for the entire cohort was 16 ± 1.8 mm. The median filter tilt angles at placement and retrieval were 5.0° (IQR, 1.8°-9°) and 4.6° (IQR, 2.1°-8.0°), respectively. The placement tilt angle was not significantly associated with complex retrieval (P = 0.59). The filter hook abutment to the vena cava wall (OR, 10.76, P = 0.003), dwell time (OR, 1.02, P = 0.029), and diameter of the vena cava (OR, 10.21, P < 0.001) were associated with complex retrieval. The diameter (P = 0.049), age (P = 0.049), and filter brand (P = 0.001) were found to be significantly associated with placement tilt., Conclusions: The inferior vena cava diameter at the time of placement predicts difficulty in filter retrieval. In addition, the filter hook abutting the inferior vena cava wall and long indwelling time may complicate retrieval. The vena cava diameter is also closely related to the degree of filter tilt., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The community population based studies on the relationship between obstructive sleep apnea and liver injury are limited. The study aimed to clarify the association between sleep apnea (SA) and liver injury by using the data in The National Health and Nutrition Examination Survey. SA was assessed by the sleep questionnaire and liver injury was evaluated by liver function test, hepatic steatosis index, and fibrosis-4. Weighted multivariable linear regression was performed to examine the association between SA and liver injury. Subgroup analyses and sensitivity analysis were also conducted. A total of 19,362 eligible participants were included in the study. After adjusting for confounders, the presence of SA was significantly associated with increased levels of lnALT, lnAST/alanine aminotransferase, lnGGT, and lnHSI (all P values < .05), but not with lnFIB-4 (P > .05). There is a dose-response relationship between the severity of SA and increased levels of lnALT, lnGGT, and decreased levels of lnAST/alanine aminotransferase (test for trend, all P values < .05). Subgroup analyses revealed that the positive association between SA and liver function, liver steatosis showed a tendency to exist in nonobese, younger, non-Hispanic Black, and male populations. Sensitive analysis showed the relationship between SA and liver injury was stable. Self-reported SA was independently associated with elevated liver enzymes and liver steatosis among US population. The association was more pronounced among nonobese, younger, non-Hispanic Black, and male populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. β-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women., Competing Interests: Declaration of competing interest The authors assert that the research was carried out without any commercial or financial associations that could be interpreted as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration., Methods: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset., Results: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis., Conclusion: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (F up ) of OTA in plasma of rat and human was 0.02-0.04% and 0.13-4.21%, respectively. In vitro experiments, the maximum enzyme velocity (V max ) and Michaelis-Menten constant (K m ) of OTA in rat and human liver microsomes were 3.86 and 78.17 μg/g min -1 , 0.46 and 4.108 μg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The attributes of good solubility and the redox-neutral nature of molten salt fluxes enable them to be useful for the synthesis of novel crystalline actinide compounds. In this work, a flux growth method under an inert atmosphere is proposed to explore the valence diversity of uranium, and a series of five uranium silicate structures, [K 3 Cl][(U VI O 2 )(Si 4 O 10 )] ( 1 ), Cs 3 [(U V O 2 )(Si 4 O 10 )] ( 2 ), K 2 [U IV (Si 2 O 7 )] ( 3 ), K 8 [(U VI O 2 )(U V O 2 ) 2 (Si 8 O 22 )] ( 4 ), and Cs 6 [U IV (U V O) 2 (Si 12 O 32 )] ( 5 ), were synthesized using different metal halide salt and feeding U/Si ratios. Crystal structure analysis reveals that the utilization of argon atmosphere that helps to avoid possible oxidation of low-valence uranium generates a variety of oxidation states of uranium including U(VI), U(V), U(IV), mixed-valence U(V) and U(VI), and mixed-valence U(IV) and U(V). Characterization of physicochemical properties of representative compounds shows that all these uranium silicate compounds have bandgaps among the range of 2.0-3.4 eV, and mixed-valence uranium silicate compounds have relatively narrower bandgaps. Density functional theory calculations on formation enthalpies, lattice energies, and bandgaps of all five compounds were also performed to provide more structural information about these uranium silicates. This work enriches the library of variable-valence uranium silicate compounds and provides a feasible way to produce novel actinide compounds with intriguing properties through the flux growth method that might show potential application in relevant fields such as storage media for nuclear waste.

Background: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research., Aim: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs., Methods: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues., Results: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues., Conclusion: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

During the PUREX process, the separation between U(VI) and Pu(IV) is achieved by reducing Pu(IV) to Pu(III), which is complicated and energy-consuming. To address this issue, we report here the first case of separation of U(VI) from Pu(IV) by o -phenanthroline diamide ligands under high acidity. Two new o -phenanthroline diamide ligands (1,10-phenanthroline-2,9-diyl)bis(indolin-1-ylmethanone) (L1) and (1,10-phenanthroline-2,9-diyl)bis((2-methylindolin-1-yl)methanone) (L2) were synthesized, which can effectively separate U(VI) from Pu(IV) even at 4 mol/L HNO 3 . The highest separation factor of U(VI) and Pu(IV) can reach over 1000, setting a new record for the separation of U(VI) from Pu(IV) under high acidity. Furthermore, extracted U(VI) can be easily recovered with water or dilute nitric acid, and the extraction performance remains stable even after 150 kGy gamma irradiation, which provides solid experimental support for potential engineering applications. The results of UV-vis titration and single-crystal X-ray diffraction measurements show that the 1:1 complex formed by L1 with U(VI) is more stable than all of the previously reported phenanthroline ligands, which reasonably reveals that the ligand L1 designed in this work has excellent affinity for U(VI). The findings of this work promise to contribute to the facilitation of the PUREX process by avoiding the use of reducing agents. It also provides new clues for designing ligands to achieve efficient separation between U(VI) and Pu(IV) at high acidity.

Objective: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation., Methods: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms., Results: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model., Conclusion: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation., (© 2024. The Author(s).)

Objective: To construct recombinant lentivirus and adenovirus which regulate the expression of c-Cbl gene and evaluate their efficacy., Methods: The interference lentivirus and overexpressed adenovirus targeting human c-Cbl gene were constructed by gene recombination technology. Quantitative PCR and western blotting were used to detect the expression changes in c-Cbl gene and its transcription after leukemia cells (HL60,THP1) were infected by virus., Results: Three recombinant interfering lentiviral vectors targeting human c-Cbl genes to successfully constructed and were identified by DNA sequencing, and the titers of the packaged viruses were all greater than 1×10 8 TU/ml. Among them, shRNA-2 lentivirus had the highest interference efficiency, and the expression of c-Cbl gene and CBL protein were decreased about 95% and 60% respectively after leukemia cells were infected with shRNA-2; In addition, the recombinant overexpression adenovirus targeting human c-Cbl gene was packaged successfully with the virus titer greater than 1×10 9 TU/ml. When leukemia cells were infected with adenovirus, the expression of c-Cbl gene and CBL protein were up-regulated about 10 times and 1.5 times respectively., Conclusion: Both recombinant interfering lentivirus and overexpression adenovirus can efficiently infect leukemia cells and affect the expressions of c-Cbl gene and CBL protein. It will lay a preliminary foundation for the subsequent study on the function of c-Cbl gene in tumor cells.

Background: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process., Methods: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect., Results: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice., Conclusions: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss., (© 2024. The Author(s).)

The construction of ecological security pattern (ESP) is of great scientific significance for solving the problem of habitat fragmentation in urban environment. However, previous studies mainly focused on the ESP in land area, leaving the sea area to be ignored. This study took the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) and its offshore area as an example and integrated the land-sea coordination into the construction of ESP based on the minimum resistance model, gravity model, and graph theory centrality. The results showed that there are 171 and 56 ecological sources for land area and offshore area, accounting for 31.46% and 21.51% of total area, respectively. Twenty-four important ecological corridors with a total length of 2738.05 km were identified in GBA, and the width is proposed to be less than 100 m. Moreover, the α, β, and γ index of the ecological network in the study area is 0.19, 1.33, and 0.5, respectively, indicating that the ecological network structure is complex and the connectivity between ecological nodes is good. The ecological restoration area includes 286.6 km 2 of ecological pinch points and 140.44 km 2 of ecological barrier. The overall ESP of the study area is "one ring, two belts, and four zones." The main body of the area with a superior ecological environment is distributed in a ring-like pattern near the outer edge of the study area, and two belts (important ecological corridor and ecological corridor) are distributed in a network. According to the ecological characteristics, the study area was divided into four zones: ecological preservation areas, ecological restoration areas, limited construction areas, and optimized construction areas. The ESP established herein institute provides a reference for the revision of ecological space control and optimization measures in the GBA. It also provides effective and systematic means to solve ecological problems in the current territorial spatial planning and territorial ecological restoration of coastal urban agglomeration., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary syndrome (PCOS). This has prompted the re-examination of the features that characterise this common condition. Current definitions have led to great heterogeneity in the prevalence of PCOS and have contributed to inconsistent treatment protocols and assessment of therapeutic outcomes. Diagnosis is further complicated by the lack of universal agreement on threshold cut-offs for ovarian dysfunction and ethnic differences in hirsutism; both of which are key features in the definitions that are commonly used currently. These challenges often result in dissatisfaction with medical care among PCOS patients and their physicians., Method: Our factor analysis mathematically identified anti-Mullerian hormone (AMH), associated polycystic ovarian morphology (PCOM) and serum testosterone as the only significant cluster associated with menstrual cycle length variability., Results and Conclusion: As such, we propose a simplified criteria wherein the presence of at least 2 of the 3 features below would be sufficient to define PCOS: (1) chronic oligo-ovulation or anovulation as indicated by oligomenorrhea (cycle lengths >35 days) or amenorrhea; (2) PCOM: raised AMH ≥37.0 pmol/L instead of transvaginal ultrasound assessment of ovaries; and (3) Androgen excess, or raised serum androgens above the laboratory reference for women. Further studies are required to examine whether the proposed criteria would reduce diagnostic confusion and improve care and outcomes, especially among patients of East Asian ethnicities., Competing Interests: This paper was first presented on 9 October 2022 as part of the 100th anniversary celebration of the NUS Department of Obstetrics and Gynaecology at Raffles Convention Centre, Singapore.

Inclusion of nanoscience in pharmaceutical education should be reinforced, in order to match the demand of current pharmaceutical talent cultivation., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although interlocked three-dimensional molecules display unique properties associated with their spatial structures, their synthesis and study of their host-guest properties remain challenging. We report the formation of a novel [2]catenane, [Et 4 N]@[(Tp*WS 3 Cu 3 Cl) 2 ( cis -bpype) 3 ] 2 (OTf) 5 ([Et 4 N][ 1 ](OTf) 5 ), by self-assembly of the cluster node [Tp*WS 3 Cu 3 Cl] + and the organic linker ( Z )-1,2-diphenyl-1,2-bis(4-(pyridin-4-yl)phenyl)ethene ( cis -bpype). Single-crystal X-ray and NMR analyses established that [ 1 ] 4+ is formed by the interpenetration of two cluster-organic cages. Unique cation-in-cation host-guest complexes were observed with this catenane. The crystalline, empty catenane was formed by taking advantage of the electrostatic repulsion-induced weak binding of the host. Encapsulation experiments also reveal that the empty catenane can adaptively encapsulate cations such as [Et 4 N] + and [Pr 4 N] + in the cross cavity but is unable to encapsulate [Bu 4 N] + and [Me 4 N] + , although the size of the latter is compatible with that of the cavity. Theoretical calculations and volume analysis allow to unravel the ingenious role of catenane structures and the interplay between electrostatic repulsion and attractive noncovalent interactions for size-specific recognition behavior in host-guest systems involving species with similar electric charges.

Nonalcoholic fatty liver disease (NAFLD) occurrence and progression are associated with lipid accumulation, insulin resistance, inflammation, liver damage, fibrosis, and other factors. AMP-dependent protein kinase (AMPK) is a key molecule that regulates bioenergy metabolism and participates in multiple biological processes, including lipid metabolism, autophagy, inflammation, and cell apoptosis. Promoting AMPK activation can reduce hepatic lipid accumulation and insulin resistance, alleviate the development of NAFLD, reduce liver inflammation and fibrosis, and inhibit the progression of NAFLD to nonalcoholic steatohepatitis.

Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34 + leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8 + T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Incomplete stent apposition has been documented after sirolimus-eluting stent implantation. However, its clinical sequelae remain controversial. To identify the incidence and its clinical consequences of ISA, IVUS was performed on 78 patients. In spite of well apposition immediately after the deployment, late stent malapposition occurred after 6-months follow-up. A total of 7 patients who received SES showed ISA. There were no significant differences in IVUS measurements between patients with or without ISA. However, there was an increase in external elastic membrane area in ISA group than non-ISA group (19.69 ± 3.50 vs. 15.05 ± 2.56 mm 2 , P<0.05). There were positive clinical events for ISA cases at 6-months clinical follow-up. Univariate and multivariable analyses indicated that hs-CRP, miR-21, and MMP-2 were risk factor for ISA. ISA was observed in 9% of patients after SES implantation, which was related to vessel positive remodeling. The incidence of MACEs in patients with ISA was higher than those without ISA. However, careful long-term follow-up remains to be clarified., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8 + T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy., (© 2023. West China Hospital, Sichuan University.)

Moisture harvesters with favourable attributes such as easy synthetic availability and good processability as alternatives for atmospheric moisture harvesting (AWH) are desirable. This study reports a novel nonporous anionic coordination polymer (CP) of uranyl squarate with methyl viologen (MV 2+ ) as charge balancing ions (named U-Squ-CP) which displays intriguing sequential water sorption/desorption behavior as the relative humidity (RH) changes gradually. The evaluation of AWH performance of U-Squ-CP shows that it can absorb water vapor under air atmosphere at a low RH of 20 % typical of the levels found in most dry regions of the world, and have good cycling durability, thus demonstrating the capability as a potential moisture harvester for AWH. To the authors' knowledge, this is the first report on non-porous organic ligand bridged CP materials for AWH. Moreover, a stepwise water-filling mechanism for the water sorption/desorption process is deciphered by comprehensive characterizations combining single-crystal diffraction, which provides a reasonable explanation for the special moisture harvesting behaviour of this non-porous crystalline material., (© 2023 Wiley-VCH GmbH.)

Its high coordination number and tendency to cluster make Th 4+ suitable for constructing metal-organic frameworks (MOFs) with novel topologies. In this work, two novel thorium-based heterometallic MOF isomers (IHEP-17 and IHEP-18) were assembled from a Th 6 cluster, a multifunctional organic ligand [4-(1 H -pyrazol-4-yl)benzoic acid (HPyba)], and Cu 2+ /Ni 2+ cations via the one-pot solvothermal synthesis strategy. The framework features a 6,12-connected new topology net and contains two kinds of supramolecular cage structures, Th 36 M 4 and Th 24 M 2 , suitable for guest exchange. Both MOF materials can efficiently adsorb I 2 . X-ray photoelectron spectroscopy, Raman spectroscopy, and single-crystal X-ray diffraction indicate that the adsorbed iodine is uniformly distributed within the Th 36 M 4 cage but not the Th 24 M 2 cage in the form of I 3 - .

Efficient transfer of charge carriers through a fast transport pathway is crucial to excellent photocatalytic reduction performance in solar-driven CO 2 reduction, but it is still challenging to effectively modulate the electronic transport pathway between photoactive motifs by feasible chemical means. In this work, we propose a thermally induced strategy to precisely modulate the fast electron transport pathway formed between the photoactive motifs of a porphyrin metal-organic framework using thorium ion with large ionic radius and high coordination number as the coordination-labile metal node. As a result, the stacking pattern of porphyrin molecules in the framework before and after the crystal transformations has changed dramatically, which leads to significant differences in the separation efficiency of photogenerated carriers in MOFs. The rate of photocatalytic reduction of CO 2 to CO by IHEP-22(Co) reaches 350.9 μmol·h -1 ·g -1 , which is 3.60 times that of IHEP-21(Co) and 1.46 times that of IHEP-23(Co) . Photoelectrochemical characterizations and theoretical calculations suggest that the electron transport channels formed between porphyrin molecules inhibit the recombination of photogenerated carriers, resulting in high performance for photocatalytic CO 2 reduction. The interaction mechanism of CO 2 with IHEP-22(Co) was clarified by using in-situ electron paramagnetic resonance, in-situ diffuse reflectance infrared Fourier transform spectroscopy, in-situ extended X-ray absorption fine structure spectroscopy, and theoretical calculations. These results provide a new method to regulate the efficient separation and migration of charge carriers in CO 2 reduction photocatalysts and will be helpful to guide the design and synthesis of photocatalysts with superior performance for the production of solar fuels.

Purpose: To evaluate the effects of bleaching combined with Er:YAG laser or Nd:YAG laser on bond strength and microleakage of resin fillings on enamel surface., Methods: Sixty-four pieces of enamel specimens prepared from isolated teeth were randomly divided into 4 groups(n=16): control group, simple bleaching group, bleaching combined with Er: YAG laser group and bleaching combined with Nd:YAG laser group. Then the shear bond strength and the depth of microleakage were tested, and the fracture mode of the specimen was observed under microscope. SPSS 26.0 software package was used for statistical analysis., Results: After bleaching simply, the bond strength of the restoration was significantly decreased, and the marginal microleakage was significantly increased(P＜0.05). There was no significant difference in shear bond strength and microleakage depth between the group bleaching combined with Er: YAG laser and control group(P＞0.05). The shear bond strength after bleaching combined with Nd:YAG laser was significantly reduced (P＜0.05), but there was no significant difference in the depth of microleakage compared with unbleached microleakage(P＞0.05). Bonding interface fracture was the main fracture mode for all groups., Conclusions: Compared to traditional bleaching, bleaching combined with laser has certain clinical advantages due to its less influence on bond strength and microleakage of resin fillings.

Objectives: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS., Methods: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test., Results: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05)., Conclusions: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1β, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke., (Copyright ® 2023 National Research University Higher School of Economics.)

Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student's t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4 + T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia . In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.

Background: Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory, thinking, language, and, eventually, the ability to carry out the simplest of tasks. Tau protein, the major component of neurofibrillary tangles, is considered a key mediator of AD pathogenesis. The association between obstructive sleep apnea (OSA) and circulating tau remains unclear. The aim of the present meta-analysis was to evaluate the relationship between OSA and circulating tau via quantitative analysis., Methods: A systematic search of Pubmed, Embase, and Web of Science were performed. The mean values of circulating total tau (T-tau) and phosphorylated tau (P-tau) in OSA and control groups were extracted. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using a random-effect model or fixed-effect model., Results: A total of seven studies comprising 233 controls and 306 OSA patients were included in this study. The meta-analysis showed that the circulating T-tau level was significantly higher in OSA patients than those in the control group (SMD = 1.319, 95% CI = 0.594 to 2.044, z = 3.56, p < .001). OSA patients also had significantly higher circulating P-tau level than control group (SMD = 0.343, 95% CI = 0.122 to 0.564, z = 3.04, p = .002)., Conclusions: The present meta-analysis demonstrated that both circulating T-tau and P-tau levels were significantly increased in OSA subjects when compared with non-OSA subjects. Larger sample-size studies on the association between OSA and circulating tau are still required to further validate our results., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota., Methods: Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests., Results: The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct β-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups., Conclusions: Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Yan, Qiao, Zheng, Niu, Huang and Pan.)

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m 6 A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

Human dental pulp stem cells (hDPSCs) are considered promising multipotent cell sources for tissue regeneration. Regulation of apoptosis and maintaining the cell homeostasis is a critical point for the application of hDPSCs. Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, was proved an important regulatory protein of hDPSCs in our previous research. Thus, the role of OMD in the apoptosis of hDPSCs was explored in this study. The expression of OMD following apoptotic induction was investigated and then the hDPSCs stably overexpressing or knocking down OMD were established by lentiviral transfection. The proportion of apoptotic cells and apoptosis-relative genes and proteins were examined with flow cytometry, Hoechst staining, Caspase 3 activity assay, qRT-PCR and western blotting. RNA-Seq analysis was used to explore possible biological function and mechanism. Results showed that the expression of OMD decreased following the apoptotic induction. Overexpression of OMD enhanced the viability of hDPSCs, decreased the activity of Caspase-3 and protected hDPSCs from apoptosis. Knockdown of OMD showed the opposite results. Mechanistically, OMD may act as a negative modulator of apoptosis via activation of the Akt/Glycogen synthase kinase 3β (GSK-3β)/β-Catenin signaling pathway and more functional and mechanistic possibilities were revealed with RNA-Seq analysis. The present study provided evidence of OMD as a negative regulator of apoptosis in hDPSCs. Akt/GSK-3β/β-Catenin signaling pathway was involved in this process and more possible mechanism detected needed further exploration. This anti-apoptotic function of OMD provided a promising application prospect for hDPSCs in tissue regeneration., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019 were included in this study. Overall survival (OS) was the primary outcome. Kaplan-Meier method was employed to detect the prognostic difference with Log-rank tests. The Cox regression analysis was performed to explore the potential prognostic factors while the multivariate Cox analysis was used to identify candidate variables for the prognostic model of OS. Results: The 5-year actuarial rates of OS, progression-free survival, loco-regional progression-free survival, and distant metastases-free survival did not show significant difference between the IMRT and RCT groups ( P  > .05). Age at recurrence and rT category were found to be the independent prognostic factors for OS. We found that rNPC patients suffered poor OS in the high-risk group (patients with higher age at recurrence and advanced rT category) (high-risk vs low-risk, HR = 1.87, 95% CI: 1.36-2.57, P  < .001). Salvage RT alone may be superior to RCT for patients in the low-risk group (RCT group vs RT group, HR = 1.89, 95% CI: 1.11-3.20, P  = .038). Conclusion: Salvage RT combined with chemotherapy cannot improve survival outcomes for rNPC. More novel clinical trials should be explored to develop individualized strategies to improve survival and minimize toxicities.

Objectives: Mutant C/EBPα p30 (mp30), the product of C/EBPα double mutations (DM), lacks transactivation domain 1 and has C-terminal loss-of-function mutation. Acute myeloid leukaemia (AML) patients harbouring C/EBPα DM could be classified as a distinct subgroup with favourable prognosis. However, the underlying mechanism remains elusive., Materials and Methods: Autophagy regulated by mp30 was detected by western blot and immunofluorescence. Immune infiltration analysis and GSEA were performed to investigate autophagic and inflammatory status of AML patients from the GSE14468 cohort. Flow cytometry was applied to analyse T cell activation., Results: Mp30 inhibited autophagy by suppressing nucleus translocation of NF-κB. Autophagy-associated secretion of IL-1β was decreased in mp30-overexpressed AML cells. Bioinformatic analysis revealed that inflammatory status was attenuated, while CD8 + T cell infiltration was upregulated in C/EBPα DM AML patients. Consistently, the proportion of CD8 + CD69 + T cells in peripheral blood mononuclear cells (PBMCs) was upregulated after co-culture with mp30 AML cell conditional culture medium. Knock-out of IL-1β in AML cells also enhanced CD8 + T cell activation. Accordingly, IL-1β expression was significantly reduced in the bone marrow (BM) cells of C/EBPα DM AML patients compared to the wildtype, while the CD8 + CD69 + T cell proportion was specifically elevated., Conclusions: C/EBPα DM alleviates immunosuppression of CD8 + T cells by inhibiting the autophagy-associated secretion of IL-1β, which elucidated that repression of autophagy-related inflammatory response in AML patients might achieve a favourable clinical benefit., (© 2022 The Authors. Cell Proliferation published by European Cell Proliferation Society and John Wiley & Sons Ltd.)

With the emergence of environmental issues regarding persistent organic pollutants (POPs), fugacity models have been widely used in the concentration prediction and exposure assessment of POPs. Based on 778 relevant research articles published between 1979 and 2020 in the Web of Science Core Collection (WOSCC), the current research progress of the fugacity model on predicting the fate and transportation of POPs in the environment was analyzed by CiteSpace software. The results showed that the research subject has low interdisciplinarity, mainly involving environmental science and environmental engineering. The USA was the most paper-published country, followed by Canada and China. The publications of the Chinese Academy of Sciences, Lancaster University, and Environment Canada were leading. Collaboration between institutions was inactive and low intensity. Keyword co-occurrence analysis showed that polychlorinated biphenyls, organochlorine pesticides, and polycyclic aromatic hydrocarbons were the most concerning compounds, while air, water, soil, and sediment were the most concerning environmental media. Through co-citation cluster analysis, in addition to the in-depth exploration of traditional POPs, research on emerging POPs such as cyclic volatile methyl siloxane and dechlorane plus were new research frontiers. The distribution and transfer of POPs in the soil-air environment have attracted the most attention, and the regional grid model based on fugacity has been gradually improved and developed. The co-citation high-burst detection showed that the research hotspots gradually shifted from pollutant persistence and long-range transport potential to pollutant distribution rules among the different environmental media and the long-distance transmission simulation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that of refractory-to-antihistamines chronic spontaneous urticaria (CSU). We retrieved interventional studies and observational studies on omalizumab efficacy to CIndU patients and efficacy comparison between CSU and CIndU both refractory to H1-antihistamines in electronic databases (accessed till May 2022). The odd ratio (OR) and 95% confidence interval (CI) was calculated with a random-effect model in this meta-analysis. The majority of patients with different CIndU subtypes gained complete or partial response and good safety after omalizumab treatment. A total of five studies with 355 CSU patients and 103 CIndU patients were included for the meta-analysis. There was no significant difference in the efficacy of omalizumab in the treatment of CSU and CIndU (OR -0.83, 95% CI [0.84, 2.21], P > 0.05). Based on the validity of omalizumab in the treatment of various CIndU subtypes and non-differential efficacy between CSU and CIndU, it is reasonable to list omalizumab as a third-line treatment of refractory CIndU., (© 2022 Wiley Periodicals LLC.)

Objectives: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS)., Methods: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS., Results: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS., Conclusions: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Objectives: To study the clinical characteristics of primary Sjögren's syndrome (pSS) with different onset age, and perform a review of the literature to confirm if the clinical phenotypes are affected by onset age in patients with pSS., Methods: Data of 742 patients with pSS were retrospectively analysed. Patients were divided into three groups according to onset age: young-onset pSS (YopSS, <35 years), adult-onset pSS (AopSS, ≥35 and ≤65 years), and elderly-onset pSS (EopSS, >65 years). Clinical characteristics were compared among three groups and further multiple comparisons were conducted by Bonferroni adjustment. The Chi-squared test for linear-by-linear association was used to explore variation tendency., Results: This study included 105 (14.2%), 533 (71.8%), and 104 (14.0%) cases of YopSS, AopSS, and EopSS, respectively. YopSS demonstrated lower prevalence of dry mouth, abnormal Schirmer I tests, and interstitial lung disease (ILD), but higher proportions of low C3 and C4 levels, and ANA, anti-SSA, anti-SSB, and rheumatoid factor (RF) positivity than AopSS and EopSS. The proportions of dry mouth (p=0.004), abnormal Schirmer I tests (p=0.002), and ILD (p<0.001) tended to increase with the increase of onset age, while the prevalence of leukopenia (p=0.011), low C3 (p=0.001), low C4 (p=0.001), and ANA (p<0.001), anti-SSA (p<0.001), anti-SSB (p<0.001) and RF (p<0.001) positivity tended to decrease with an increase in onset age., Conclusions: YopSS demonstrated less dryness and ILD, but more immunologic disorders. ILD prevalence were directly proportional to onset age of pSS; however, leukopenia, hypocomplementaemia, and autoantibody positivity showed opposite trends.