CORM-3 Inhibits the Inflammatory Response of Human Periodontal Ligament Fibroblasts Stimulated by LPS and High Glucose.

Introduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages. Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats. Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats. Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Cyclodextrin-based metal-organic frameworks transforming drug delivery.

Cyclodextrin-based metal-organic frameworks (CD-MOFs) are gaining traction in the realm of drug delivery due to their inherent versatility and potential to amplify drug efficacy, specificity, and safety. This article explores the predominant preparation techniques for CD-MOFs, encompassing methods like vapor diffusion, microwave-assisted, and ultrasound hydrothermal approaches. Native CD-MOFs present compelling advantages in drug delivery applications. They can enhance drug loading capacity, stability, solubility, and bioavailability by engaging in diverse interactions with drugs, including host-guest, hydrogen bonding, and electrostatic interactions. Beyond their inherent properties, CD-MOFs can be customized as drug carriers through two primary strategies: co-crystallization with functional components and surface post-modifications. These tailored modifications pave the way for controlled release manners. They allow for slow and sustained drug release, as well as responsive releases triggered by various factors such as pH levels, glutathione concentrations, or specific cations. Furthermore, CD-MOFs facilitate targeted delivery strategies, like pulmonary or laryngeal delivery, enhancing drug delivery precision. Overall, the adaptability and modifiability of CD-MOFs underscore their potential as a versatile platform for drug delivery, presenting tailored solutions that cater to diverse biomedical and industrial needs.

Gestational diabetes mellitus affects the differentiation of hematopoietic stem cells in neonatal umbilical cord blood.

PURPOSE: There are abundant hematopoietic stem cells (HSCs) in cord blood. It is known that HSCs continue to differentiate to CLP, CMP and erythroid progenitor cells (EPC), EPC ultimately differentiated to platelets and erythrocytes. It has been reported that the proportion of HSCs in cord blood was higher than that in healthy pregnant women, so as the incidence of neonatal polycythemia in gestational diabetes mellitus (GDM) patients. We aimed to investigate whether the hyperglycemic and/or hyperinsulin environment in GDM patients has effects on the differentiation of HSCs into erythrocytes in offspring cord blood. METHODS: In this study, we collected cord blood from 23 GDM patients and 52 healthy pregnant women at delivery. HSCs, CLP, CMP and EPCs in cord blood of the two groups were identified and quantified by flow cytometry. HSCs were sorted out and treated with glucose and insulin, respectively, and then, the changes of HSCs proliferation and differentiation were detected. RESULTS: Compared to healthy controls, HSCs, CMP and EPC numbers in cord blood from GDM group were significantly increased, while CLP cell number was decreased. The differentiation of HSCs into EPC was promoted after treatment with glucose or insulin. CONCLUSION: There were more HSCs in the cord blood of GDM group, and the differentiation of HSCs to EPCs was increased. These findings were probably caused by the high-glucose microenvironment and insulin medication in GDM patients, and the HSCs differentiation changes might be influencing factors of the high incidence of neonatal erythrocytosis in GDM patients.

In Silico Evaluation of In Vivo Degradation Kinetics of Poly(Lactic Acid) Vascular Stent Devices.

Biodegradable vascular stents (BVS) are deemed as great potential alternatives for overcoming the inherent limitations of permanent metallic stents in the treatment of coronary artery diseases. The current study aimed to comprehensively compare the mechanical behaviors of four poly(lactic acid) (PLA) BVS designs with varying geometries via numerical methods and to clarify the optimal BVS selection. Four PLA BVS (i.e., Absorb, DESolve, Igaki-Tamai, and Fantom) were first constructed. A degradation model was refined by simply including the fatigue effect induced by pulsatile blood pressures, and an explicit solver was employed to simulate the crimping and degradation behaviors of the four PLA BVS. The degradation dynamics here were characterized by four indices. The results indicated that the stent designs affected crimping and degradation behaviors. Compared to the other three stents, the DESolve stent had the greatest radial stiffness in the crimping simulation and the best diameter maintenance ability despite its faster degradation; moreover, the stent was considered to perform better according to a pilot scoring system. The current work provides a theoretical method for studying and understanding the degradation dynamics of the PLA BVS, and it could be helpful for the design of next-generation BVS.

Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.

Supramolecular Annihilator with DPA Parallelly Arranged by Multiple Hydrogen-Bonding Interactions for Enhanced Triplet-Triplet Annihilation Upconversion.

The triplet annihilator is a critical component for triplet-triplet annihilation upconversion (TTA-UC); both the photophysical properties of the annihilator and the intermolecular orientation have pivotal effects on the overall efficiency of TTA-UC. Herein, we synthesized two supramolecular annihilators A-1 and A-2 by grafting 9,10-diphenylanthracene (DPA) fragments, which have been widely used as triplet annihilators for TTA-UC, on a macrocyclic host-pillar[5]arenes. In A-1, the orientation of the two DPA units was random, while, in A-2, the two DPA units were pushed to a parallel arrangement by intramolecular hydrogen-bonding interactions. The two compounds showed very similar photophysical properties and host-guest binding affinities toward electron-deficient guests, but showed totally different TTA-UC emissions. The UC quantum yield of A-2 could be optimized to 13.7% when an alkyl ammonia chain-attaching sensitizer S-2 was used, while, for A-1, only 5.1% was achieved. Destroying the hydrogen-bonding interactions by adding MeOH to A-2 significantly decreased the UC emissions, demonstrating that the parallel orientations of the two DPA units contributed greatly to the TTA-UC emissions. These results should be beneficial for annihilator designs and provide a new promising strategy for enhancing TTA-UC emissions.

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis.

Purpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71. Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot. Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts. Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.

Functional Plasticity, Redundancy, and Specificity of Lanosterol 14α-Demethylase in Regulating the Sensitivity to DMIs in Calonectria ilicicola.

Cytochrome P450 sterol 14α-demethylase (CYP51) is a key enzyme involved in the sterol biosynthesis pathway and serves as a target for sterol demethylation inhibitors (DMIs). In this study, the 3D structures of three CPY51 paralogues from Calonectria ilicicola (C. ilicicola) were first modeled by AlphaFold2, and molecular docking results showed that CiCYP51A, CiCYP51B, or CiCYP51C proteins individually possessed two active pockets that interacted with DMIs. Our results showed that the three paralogues play important roles in development, pathogenicity, and sensitivity to DMI fungicides. Specifically, CiCYP51A primarily contributed to cell wall integrity maintenance and tolerance to abiotic stresses, and CiCYP51B was implicated in sexual reproduction and virulence, while CiCYP51C exerted negative regulatory effects on sterol 14α-demethylase activity within the ergosterol biosynthetic pathway, revealing its genus-specific function in C. ilicicola. These findings provide valuable insights into developing rational strategies for controlling soybean red crown rot caused by C. ilicicola.

Resistance mechanism of Phomopsis longicolla to fludioxonil is associated with modifications in PlOS1, PlOS4 and PlOS5.

Phomopsis longicolla, a causal agent of soybean root rot, stem blight, seed decay, pod and stem canker, which seriously affects the yield and quality of soybean production worldwide. The phenylpyrrole fungicide fludioxonil exhibits a broad spectrum and high activity against phytopathogenic fungi. In this study, the baseline sensitivity of 100 P. longicolla isolates collected from the main soybean production areas of China to fludioxonil were determined. The result showed that the EC50 values of all the P. longicolla isolates ranged from 0.013 to 0.035 µg/ml. Furthermore, 12 fludioxonil-resistance (FluR) mutants of P. longicolla were generated from 6 fludioxonil-sensitive (FluS) isolates. and the resistance factors (RF) of 12 FluR mutants were >3500. Sequence alignment showed that multiple mutation types were found in PlOS1, PlOS4 or/and PlOS5 of FluR mutants. All the FluR mutants exhibited fitness penalty in mycelial growth, conidiation, virulence and osmo-adaptation. Under fludioxonil or NaCl treatment condition, the glycerol accumulation was significantly increased in FluS isolates, but was slightly increased in FluR mutants, and the phosphorylation level of most FluR mutants was significantly decreased when compared to the FluS isolates. Additionally, positive cross-resistance was observed between fludioxonil and procymidone but not fludioxonil and pydiflumetofen, pyraclostrobin or fluazinam. This is first reported that the baseline sensitivity of P. longicolla to fludioxonil, as well as the biological and molecular characterizations of P. longicolla FluR mutants to fludioxonil. These results can provide scientific directions for controlling soybean diseases caused by P. longicolla using fludioxonil.

Functional Differentiation of the Succinate Dehydrogenase Subunit SdhC Governs the Sensitivity to SDHI Fungicides, ROS Homeostasis, and Pathogenicity in Fusarium asiaticum.

Succinate dehydrogenase (SDH) is an integral component of the tricarboxylic acid cycle (TCA) and respiratory electron transport chain (ETC), targeted by succinate dehydrogenase inhibitors (SDHIs). Fusarium asiaticum is a prominent phytopathogen causing Fusarium head blight (FHB) on wheat. Here, we characterized the functions of the FaSdhA, FaSdhB, FaSdhC1, FaSdhC2, and FaSdhD subunits. Deletion of FaSdhA, FaSdhB, or FaSdhD resulted in significant growth defects in F. asiaticum. The FaSdhC1 or FaSdhC2 deletion mutants exhibited substantial reductions in fungal growth, conidiation, virulence, and reactive oxygen species (ROS). The FaSdhC1 expression was significantly induced by pydiflumetofen (PYD). The ΔFaSdhC1 mutant displayed hypersensitivity to SDHIs, whereas the ΔFaSdhC2 mutant exhibited resistance against most SDHIs. The transmembrane domains of FaSdhC1 are essential for regulating mycelial growth, virulence, and sensitivity to SDHIs. These findings provided valuable insights into how the two SdhC paralogues regulated the functional integrity of SDH, ROS homeostasis, and the sensitivity to SDHIs in phytopathogenic fungi.

ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.

The HOG-pathway related AaOS1 leads to dicarboximide-resistance in field strains of Alternaria alternata and contributes, together with the Aafhk1, to mycotoxin production and virulence.

BACKGROUND: Garlic leaf spot (GLS) caused by Alternaria alternata is one of the main diseases in the garlic production areas, and its management heavily relies on dicarboximide fungicides. However, the efficacy of dicarboximides against the GLS disease has decreased year on year. RESULTS: In the present study, 10 of 148 A. alternata strains separated from Jiangsu Province were moderately resistant (MR) to a dicarboximide fungicide procymidone (ProMR). Positive cross-resistance was observed between Pro and iprodione (Ipro) or fludioxonil (Fld), but not between Pro and fluazinam or azoxystrobin. Mutations at AaOS1, but not Aafhk1, were confirmed to confer the Pro resistance by constructing replacement mutants, whereas mutations at both AaOS1 and Aafhk1 decreased the gene expression level of AapksI, as well as the ability to produce mycotoxin AOH (polyketide-derived alternariol) and virulence. Additionally, more genes (AaOS1 and Aafhk1) harboring the mutations experienced a larger biological fitness penalty. CONCLUSION: To our knowledge, this is the first report on Pro resistance selected in garlic fields, and mutations at AaOS1 of A. alternata causing a decreased ability to produce the mycotoxin AOH. © 2024 Society of Chemical Industry.

A phenomenological model of pulsatile blood pressure-affected degradation of polylactic acid (PLA) vascular stent.

The stent implantation may alter the post-operative patient's blood pressure, and bioresorbable vascular stents (BVS) as a candidate to treat vascular diseases, its degradation is affected by mechanical stress, thus, the altered pressure representing varying stress level will result in different degradation behaviors of the BVS. This paper first proposed a novel stress-regulated PLA degradation model that included swelling factor, and then the degradation evolutions of a PLA BVS within 180 days under normal and high blood pressures were simulated by finite element method, and more four degradation indexes were defined to study the effects of the two blood pressures on the degradation of the PLA BVS. The results showed that the high pressure weakly accelerated the degradation of the PLA BVS with respect to the normal pressure by examining the four indexes, e.g., the residual stent volume v r ( t ) decreased to 0.72 and 0.69, respectively for the normal and high pressures at day 180. The current finding provided a theoretical understanding of the PLA BVS degradation, and hinted that the PLA BVS may not need to be elaborately selected in clinical practices for treating hypertensive patients.

Factors influencing spiritual wellbeing among pancreatic ductal adenocarcinoma patients receiving chemotherapy.

BACKGROUND: Spiritual wellbeing emphasizes optimistic and positive attitudes while self-regulating negative emotions when coping with stress. However, there have only been a few small studies of spiritual wellbeing of pancreatic ductal adenocarcinoma (PDAC) patients undergoing chemotherapy. The core factors influencing spiritual wellbeing in this clinical population are still unclear. AIM: To identify factors influencing spiritual wellbeing among patients with PDAC receiving chemotherapy. METHODS: A total of 143 PDAC patients receiving chemotherapy were enrolled from January to December 2022. Patients completed general information questionnaires including: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 Item Scale (FACIT-Sp-12), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Zung's Self-rating Anxiety Scale (SAS). Independent sample t-test, one-way analysis of variance, Pearson's correlation analysis, and multiple linear regression analysis were adopted for statistical analyses. P < 0.05 (two-tailed) was considered statistically significant for all tests. RESULTS: Total spiritual wellbeing (FACIT-Sp-12) score was 32.16 ± 10.06 points, while dimension sub-scores were 10.85 ± 3.76 for faith, 10.55 ± 3.42 for meaning, and 10.76 ± 4.00 for peace. Total spiritual wellbeing score was negatively correlated with SAS score for anxiety and with the symptom domain of EORTC QLC-C30. Conversely, spiritual wellbeing score was positively correlated with global health status and EORTC QLQ-C30 role functioning domain score. Multivariate regression analysis identified educational level, health insurance category, symptom domain, functional role domain, and global health status as significant independent factors influencing spiritual wellbeing among PDAC patients undergoing chemotherapy (R2 = 0.502, P < 0.05). CONCLUSION: Individualized spiritual support is needed for PDAC patients. Health, daily functioning, emotional, cognitive, and social function status should be taken into account to promote implementation of spirituality in nursing practice.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus: A meta-analysis.

OBJECTIVE: To determine the risk factors of pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) through systematic reviews and meta-analyses. METHODS: We undertook electronic search strategies using Medline via PubMed, Embase, Web of Science, and Cochrane Library up to April 11, 2023. Study selection and data extraction were performed by 2 authors independently. We made risk of bias judgments based on the Newcastle-Ottawa Scale (NOS). Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to estimate the overall effect sizes of potential risk factors for PAH in SLE patients. Univariate and multivariate meta-regression models were used to assess the independent effects of each risk factor on PAH. Sensitivity analyses were also conducted to explore potential sources of heterogeneity. RESULTS: A total of 19 articles were included in this meta-analysis, and the results showed that gender (female) [RR = 1.04, 95% CI (1.02, 1.06), p = .0001], interstitial lung disease [RR = 4.36, 95% CI (2.42, 7.85), p = .0001], alopecia [RR = 1.39, 95% CI (1.06, 1.83), p = .017], Raynaud's phenomenon [RR = 1.83, 95% CI (1.41, 2.37), p = .0001], systemic hypertension [RR = 1.30, 95% CI (1.07, 1.58), p = .007], serositis [RR = 2.29, 95% CI (1.89, 2.77), p = .0001], pericardial effusion [RR = 3.33, 95% CI (2.20, 5.05), p = .0001], anti-RNP [RR = 1.86, 95% CI (1.19, 2.91), p = .006], anti-SSA [RR = 1.28, 95% CI (1.01, 1.62), p = .041], anti-SSB [RR = 1.38, 95% CI (1.19, 1.60), p = .0001], anti-U1RNP [RR = 1.58, 95% CI (1.07, 2.34), p = .023], thrombocytopenia [RR = 1.38, 95% CI (1.14, 1.68), p = .001], and current smokers [RR = 2.20, 95% CI (1.19, 4.06), p = .012] were all risk factors for PAH related to SLE. CONCLUSION: PAH is a serious complication of SLE. Since prognosis of SLE patients after the occurrence of PAH is poor, routine examination should be conducted for SLE patients with PAH risk factors.

Integrated Full-Length Transcriptome and Metabolome Profiling Reveals Flavonoid Regulation in Response to Freezing Stress in Potato.

Cold stress impairs plant growth and development, resulting in crop failure. Cultivated potato (Solanum tuberosum L.) is sensitive to freezing, while its wild relative, S. commersonii, has a strong freezing tolerance. To decipher the anti-freezing mechanism of CM, we carried out a transcriptomic and metabolomic analysis of an anti-freezing variety of CM (a type of S. commersonii) and a freeze-sensitive variety of DM (a type of Solanum tuberosum L.). A total of 49,232 high-quality transcripts from 12,811 gene loci, including 46,772 coding sequences and 2018 non-coding RNAs, were identified. KEEG enrichment analysis of differentially expressed genes (DEGs) between the two varieties showed that the flavonoid biosynthesis pathway was strongly induced by freezing stress, which was proven by flavonoid metabolome analysis. Consistent with the accumulation of more flavonoids, nearly all the pathway genes were significantly upregulated in CM than those in DM. The transcript levels of two chalcone synthase (CHS-1) isoforms and four isoforms of flavonoid 3'-hydroxylase (F3'H-1) were confirmed by qRT-PCR. Co-expression analysis identified one Myb-related and three UGTs (UDP-glycosyltransferase) that were significantly upregulated in CM during freezing stress. Our findings support that the flavonoid pathway was significantly enhanced by freezing stress and the greater accumulation ofglycosylatedflavonoids in resistant types than that of sensitive types, maybe accounting for the increased freezing tolerance of freeze-resistant potato varieties.

Spiritual Well-being and Quality of Life for Patients Undergoing Chemotherapy for Pancreatic Cancer: Correlates and Influencing Factors.

Context: Pancreatic cancer (PC) is one of the most malignant digestive cancers, characterized by a poor prognosis. PC patients receiving chemotherapy can endure immense physical and psychological pain, negatively impacting spiritual well-being and QoL. Objective: The study intended to investigate PC patients' statuses regarding spiritual well-being and QoL, to identify and analyze the influencing factors, and to develop feasible spiritual-care plans, which could provide a reference for clinicians in promoting the spiritual well-being and QoL of PC chemotherapy patients. Design: The research team performed a prospective survey. Setting: The study took place at the Second Affiliated Hospital of the Army Medical University in Chongqing, China. Participants: Participants were 120 patients who underwent chemotherapy for pancreatic cancer (PC) at the hospital between November 2020 and April 2022. The research team selected participants using convenience sampling. Outcome Measures: The outcome measures included: (1) a self-designed questionnaire to identify participants' demographic and clinical characteristics and (2) the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being Scales (FACIT-Sp). The research team used the FACIT-Sp's two subscales, FACT-G and the FACIT-Sp-12, to evaluate participants' quality of life (QoL) and spiritual well-being, respectively. Results: The total scores for participants' spiritual well-being and QoL were 26.2 ± 5.39 and 65.44 ± 17.1, respectively. Spiritual well-being was positively correlated with the QoL (P < .001). According to the multiple linear regression analysis, the main factors influencing spiritual well-being were age (P < .01), education level (P < .001), average monthly income per capita of the family (P < .001), recurrence (P < .001), and pain (P < .05). The main factors influencing QoL were age (P = .008), education level (P < .001), average monthly income per capita of the family (P < .001), recurrence (P < .001), and pain (P < .01). Conclusions: Patients who undergo chemotherapy for PC experience a low-to-medium level of spiritual well-being and a medium level of QoL. The detrimental factors include: (1) being middle-aged, (2) having a low education level, (3) having a low family income, (4) suffering a recurrence of the disease, and (5) experiencing moderate-to-severe pain. Medical practitioners should provide extra care and support to protect the spiritual well-being of these patients and ultimately improve their QoL.

Spatial distribution of floating population in Beijing, Tianjin and Hebei Region and its correlations with synergistic development.

Utilizing statistical information from the Seventh National Population Census, statistical yearbook and sampling dynamic survey data, this study examines the distribution characteristics of the floating population in Beijing, Tianjin and Hebei Region as well as the growth trend of the floating population in each region. It also makes assessments using floating population concentration and The Moran Index Computing Methods. According to the study, the spatial distribution of the floating population has a clear clustering pattern in Beijing, Tianjin and Hebei region. Beijing, Tianjin and Hebei region's mobile population growth patterns differ substantially, and the region's inflow population is mostly made up of migrant inhabitants of domestic provinces and inflow of people from nearby regions. Most of the mobile population resides in Beijing and Tianjin, whereas the outflow of people originates in Hebei province. The diffusion impact and the spatial features of the floating population in the Beijing, Tianjin and Hebei area have a constant, positive association, according to the timeline between 2014 and 2020.