Breast cancer colonization by Malassezia globosa accelerates tumor growth.

Malassezia globosa is a lipophilic basidiomycetous yeast that occurs abundantly in breast tumors and that may contribute to a shortened overall survival of breast cancer (BRAC) patients, suggesting that the yeast may participate in the carcinogenesis of BRAC. However, the mechanisms involved in the M. globosa-based acceleration of BRAC are unknown. Here, we show that M. globosa can colonize mammary tissue in 7,12-dimethylbenz[a] anthracene-induced mice. The abundance of M. globosa shortened the overall survival and increased the tumor incidence. Transcriptome data illustrated that IL-17A plays a key role in tumor growth due to M. globosa colonization, and tumor-associated macrophage infiltration was elevated during M. globosa colonization which triggers M2 polarization of macrophages via toll-like receptors 4/nuclear factor kappa-B (Nf-κB) signaling. Our results show that the expression of sphingosine kinase 1 (Sphk1) is increased in breast tumors after inoculation with M. globosa. Moreover, we discovered that Sphk1-specific small interfering RNA blocked the formation of lipid droplets, which can effectively alleviate the expression of the signal transducer and activator of the transcription 3 (STAT3)/Nf-κB pathway. Taken together, our results demonstrate that M. globosa could be a possible factor for the progression of BRAC. The mechanisms by which M. globosa promotes BRAC development involve the IL-17A/macrophage axis. Meanwhile, Sphk1 overexpression was induced by M. globosa infection, which also promoted the proliferation of MCF-7 cells.IMPORTANCELiterature has suggested that Malassezia globosa is associated with breast tumors; however, this association has not been confirmed. Here, we found that M. globosa colonizes in breast fat pads leading to tumor growth. As a lipophilic yeast, the expression of sphingosine kinase 1 (Sphk1) was upregulated to promote tumor growth after M. globosa colonization. Moreover, the IL-17A/macrophages axis plays a key role in mechanisms involved in the M. globosa-induced breast cancer acceleration from the tumor immune microenvironment perspective.

Nanoarchitectonics of Methyl and Aldehyde Group-Decorated SOD-Type Metal-Azolate Framework for SF6 Capture and Recovery.

Sulfur hexafluoride (SF6) is widely used as an insulating gas, being an etchant and contrast agent in the electrical, semiconductor, and medical industries. However, due to its long lifetime and high global warming potential in the atmosphere, SF6 must be carefully handled to prevent leakage during production and usage. Herein, we report a sod-net metal-azolate framework (MAF) named MAF-stu-111, which decorates methyl and aldehyde groups in the porous windows, showing high adsorption affinity for SF6 at low pressure. Stability tests, gas adsorption, and breakthrough experiments demonstrated that MAF-stu-111 possesses excellent water and chemical stability, fully reversible SF6 uptake, high SF6/N2 separation selectivity (10:90, 285.2), good reusability, and high SF6 recovery purity (99.03%). Theoretical calculations revealed that hydrogen atoms of methyl and aldehyde groups can form multiple hydrogen bonds with SF6 molecules, which ensure that SF6 molecules are firmly held within the MAF-stu-111 framework, playing a key role in the selective separation of SF6/N2.

Effects of the extraction temperatures on the protein contents, gelatin purities, physicochemical properties, and functional properties of tilapia scale gelatins.

Herein, the effects of the extraction temperatures (45, 55, 65, 75, and 85 °C) on the protein contents, gelatin purities, physicochemical properties, and functional properties of tilapia scale gelatins were studied. Among these temperatures, 65 °C was the best extraction temperature to obtain good production yield (16.0 % ± 0.3 %), good protein contents (excellent total amino acid composition of 94.20 ± 0.76 g/100 g of gelatin, the highest hydrophobic amino acids percentage of 32.68 ± 0.24 g/100 g of gelatin), appropriate ATR-FTIR spectra peaks (Amides A, B, I, II, and III), high ß-sheet percentage (38.2 % ± 1.3 %), the highest purity of the gelatin structures (280, 140, and 125 kDa), the lowest nanoparticle sizes in atomic force microscopy results, the highest water-holding capacity (25.3 % ± 0.9 %), the highest fat-binding capacity (16.9 % ± 0.1 %), high foaming properties (foaming capacity of 151.7 % ± 7.6 % and foaming stability of 145.8 % ± 6.3 %), the lowest interfacial tension (2.1 ± 0.2 mN/m), the lowest emulsifying activity index (16.5 % ± 0.9 %), the highest emulsifying stability index (88.9 % ± 5.1 %), highest emulsion viscosity (1462 ± 17 mPa·s at the rotary speed of 6 rpm), the lowest initial droplet sizes, and lowest emulsion creaming index (6.9 % ± 0.7 %). This work provided a useful guide to choosing extraction temperature for gelatin extraction and a useful theory on the relationship between compositions and properties of a protein sample.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors.

BACKGROUND: Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI. AIM: This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex. METHODS: A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis. RESULTS: The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037). CONCLUSION: The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.

Latent profile analysis of Eysenck's personality dimensions and psychological constructs in university students.

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters. Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs. Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles. Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p < 0.001, η2 = 0.163), meaning in life (F = 17.764, p < 0.001, η2 = 0.070), and positive coping (F = 40.765, p < 0.001, η2 = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty (F = 13.854, p < 0.001, η2 = 0.056) and state anxiety (F = 26.279, p < 0.001, η2 = 0.101). Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups.

Tilapia head gelatins to stabilize fish oil emulsions and the effect of extraction methods.

The preparation and use of gelatins from fish by-products have attracted much attention in the field of food science. Herein, four types of tilapia head gelatins were extracted and characterized: hot water-pretreated gelatin (HWG), acetic acid-pretreated gelatin (AAG), sodium hydroxide-pretreated gelatin (SHG), and pepsin enzyme-pretreated gelatin (PEG). The gel strength values followed the order: PEG (74 ± 1 Bloom) > AAG (66 ± 1) > HWG (59 ± 1) > SHG (34 ± 1). The foaming properties, fish oil emulsion viscosity, emulsion activity, and emulsion stabilization ability followed this order: PEG > HWG ≥ AAG > SHG. The effect mechanisms of extraction methods and gelatin concentrations on the emulsion stability involved the interfacial tension, emulsion viscosity, and fat-binding capacity. This work provided important knowledge for analyzing the relations between the structure and function of gelatin. It also provided a high-value application method of fish wastes.

Electroacupuncture protects the intestinal mucosal barrier in diarrhea-predominant Irritable Bowel Syndrome rats by regulating the MCs/Tryptase/PAR-2/MLCK pathway.

OBJECTIVE: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. METHODS: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. RESULTS: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). CONCLUSION: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.

Molecular modification of low-dissolution soy protein isolates by anionic xanthan gum, neutral guar gum, or neutral konjac glucomannan to improve the protein dissolution and stabilize fish oil emulsion.

Herein, the effects of anionic xanthan gum (XG), neutral guar gum (GG), and neutral konjac glucomannan (KGM) on the dissolution, physicochemical properties, and emulsion stabilization ability of soy protein isolate (SPI)-polysaccharide conjugates were studied. The SPI-polysaccharide conjugates had better water dissolution than the insoluble SPI. Compared with SPI, SPI-polysaccharide conjugates had lower ß-sheet (39.6 %-56.4 % vs. 47.3 %) and α-helix (13.0 %-13.2 % vs. 22.6 %) percentages, and higher ß-turn (23.8 %-26.5 % vs. 11.0 %) percentages. The creaming stability of SPI-polysaccharide conjugate-stabilized fish oil-loaded emulsions mainly depended on polysaccharide type: SPI-XG (Creaming index: 0) > SPI-GG (Creaming index: 8.1 %-21.2 %) > SPI-KGM (18.1 %-40.4 %). In addition, it also depended on the SPI preparation concentrations, glycation times, and glycation pH. The modification by anionic XG induced no obvious emulsion creaming even after 14-day storage, which suggested that anionic polysaccharide might be the best polysaccharide to modify SPI for emulsion stabilization. This work provided useful information to modify insoluble proteins by polysaccharides for potential application.

Four-year variation in pathogen distribution and antimicrobial susceptibility of urosepsis: a single-center retrospective analysis.

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis. Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment. Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years. Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year (p < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective. Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli, Enterococcus, and Klebsiella pneumoniae. If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum ß-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue.

Fish oil-loaded multicore submillimeter-sized capsules prepared with monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending.

In order to load fish oil for potential encapsulation of fat-soluble functional active substances, fish oil-loaded multicore submillimeter-sized capsules were prepared with a combination method of three strategies (monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending). The chitosan-tripolyphosphate/Tween (20, 40, 60, and 80) capsules had smaller and evener fish oil cores than the chitosan-tripolyphosphate capsules, which resulted from that Tween addition induced smaller and evener fish oil droplets in the emulsions. Tween addition decreased the water contents from 56.6 % to 35.0 %-43.4 %, increased the loading capacities from 10.4 % to 12.7 %-17.2 %, and increased encapsulation efficiencies from 97.4 % to 97.8 %-99.1 %. In addition, Tween addition also decreased the highest peroxide values from 417 meq/kg oil to 173-262 meq/kg oil. These properties' changes might result from the structural differences between the chitosan-tripolyphosphate and chitosan-tripolyphosphate/Tween capsules. All the results suggested that the obtained chitosan-tripolyphosphate/Tween capsules are promising carriers for fish oil encapsulation. This work also provided useful knowledge to understand the preparation, structural, and physicochemical properties of the chitosan-tripolyphosphate capsules.

Identification of key pathways and mRNAs in interstitial cystitis/bladder pain syndrome treatment with quercetin through bioinformatics analysis of mRNA-sequence data.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. METHODS: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. RESULTS: QCT treatment significantly decreased the level of MPO, IL-1ß, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1ß, IL-6 and TNF-α. CONCLUSION: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.

Cognitive control in honesty and dishonesty under different conflict scenarios: insights from reaction time.

This study investigated the role of cognitive control in moral decision-making, focusing on conflicts between financial temptations and the integrity of honesty. We employed a perceptual task by asking participants to identify which side of the diagonal contained more red dots within a square to provoke both honest and dishonest behaviors, tracking their reaction times (RTs). Participants encountered situations with no conflict, ambiguous conflict, and clear conflict. Their behaviors in the clear conflict condition categorized them as either "honest" or "dishonest." Our findings suggested that, in ambiguous conflict situations, honest individuals had significantly longer RTs and fewer self-interest responses than their dishonest counterparts, suggesting a greater need for cognitive control to resolve conflicts and a lesser tendency toward self-interest. Moreover, a negative correlation was found between participants' number of self-interest responses and RTs in ambiguous conflict situations (r = -0.27 in study 1 and r = -0.66 in study 2), and a positive correlation with cheating numbers in clear conflict situations (r = 0.36 in study 1 and r = 0.82 in study 2). This suggests less cognitive control was required for self-interest and cheating responses, bolstering the "Will" hypothesis. We also found that a person's self-interest tendency could predict their dishonest behavior. These insights extend our understanding of the role of cognitive control plays in honesty and dishonesty, with potential applications in education, policy-making, and business ethics.

Effects of polyphenol and gelatin types on the physicochemical properties and emulsion stabilization of polyphenol-crosslinked gelatin conjugates.

Herein, six types of polyphenol-crosslinked gelatin conjugates (PGCs) with ≥ two gelatin molecules were prepared using a covalent crosslinking method with two types of polyphenols (tannic acid and caffeic acid) and three types of gelatins (bovine bone gelatin, cold water fish skin gelatin, and porcine skin gelatin) for the emulsion stabilization. The structural and functional properties of the PGCs were dependent on both polyphenol and gelatin types. The storage stability of the conjugate-stabilized emulsions was dependent on the polyphenol crosslinking, NaCl addition, and heating pretreatment. In particular, NaCl addition promoted the liquid-gel transition of the emulsions: 0.2 mol/L > 0.1 mol/L > 0.0 mol/L. Moreover, NaCl addition also increased the creaming stability of the emulsions stabilized by PGCs except tannic acid-crosslinked bovine bone gelatin conjugate. All the results provided useful knowledge on the effects of molecular modification and physical processing on the properties of gelatins.

Effects of gelatin type and concentration on the preparation and properties of freeze-dried fish oil powders.

The effects of gelatin type (porcine skin gelatin, PSG; bovine skin gelatin, BSG; fish gelatin, FG; or cold-water fish skin gelatin, CFG) and concentration on the preparation and properties of fish oil powders were investigated in this work. The oil powders were prepared using the combination method of gelatin-sodium hexametaphosphate complex coacervation with starch sodium octenyl succinate (SSOS)-aided freeze-drying. Compared with the other gelatins, CFG-with an unobvious isoelectric point, a lower molecular weight, more hydrogen bonds, and longer gel formation time-could not form complex coacervates, which are necessary to prepare oil powders. For oil powders obtained from the other gelatins, gelatin type and concentration did not have obvious effects on microscale morphologies; they did, however, have significant effects on physicochemical properties. The highest peroxide values of the oil powders were mainly dependent on the gelatins, expressed in the following manner: PSG (153 ± 5 - 168 ± 3 meq/Kg oil) < BSG (176 ± 5 - 188 ± 1 meq/Kg oil) < FG (196 ± 11 - 201 ± 22 meq/Kg oil). Acidic and neutral pH could not dissolve the complex coacervates. However, the oil powders could be quickly dissolved to form emulsion droplets in the gastric phase, and that SSOS increased coacervate stability and promoted oil digestion during the in vitro gastrointestinal process. In sum, this study contributes fundamental information to understanding the development of fish oil solid encapsulation preparations.

Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis.

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.

Health-related quality of life in Chinese SLE patients: evidence from 1568 SLE patients and 2610 healthy controls.

OBJECTIVE: To investigate the effects of systemic lupus erythematosus (SLE) on health-related quality of life (HRQOL), the relationship between disease activity and HRQOL, and potential factors affecting HRQOL in Chinese SLE patients. METHODS: This study recruited 1568 patients and 2610 controls to explore the effects of SLE on HRQOL. The association between disease activity and HRQOL, and the influencing factors of HRQOL were determined in 1568 patients. Then, we prospectively followed 1096 patients to explore the association between reduced disease activity and improved HRQOL, and the influencing factors of improved HRQOL. The Short-Form 36 (SF-36) and SLE disease activity index (SLEDAI) were used to evaluate HRQOL and disease activity. RESULTS: Chinese SLE patients had lower HRQOL than controls in all domains (P < 0.001), especially in role-physical (RP) and role-emotional (RE). Compared with SLE patients from outside China, the HRQOL of Chinese patients appeared to be higher in mental component summary (MCS) but lower in RP and RE. SLEDAI was negatively correlated with HRQOL, which was validated using the results of a follow-up study, where SLEDAI reduction was positively associated with HRQOL improvements (P < 0.05). Furthermore, personality, life nervous and experiences of adverse life events may influence HRQOL and HRQOL improvements. CONCLUSION: SLE significantly affected the HRQOL of Chinese patients, especially in RP and RE. Disease activity was negatively correlated with HRQOL. We also found for the first time some factors affecting HRQOL, which can be regarded as the basis for improving the HRQOL of SLE patients.

The application of human-derived cell lines in neurotoxicity studies of environmental pollutants.

As industrial and societal advancements progress, an increasing number of environmental pollutants linked to human existence have been substantiated to elicit neurotoxicity and developmental neural toxicity. For research in this field, human-derived neural cell lines have become excellent in vitro models. This study examines the utilization of immortalized cell lines, specifically the SH-SY5Y human neuroblastoma cell line, and neural cells derived from human pluripotent stem cells, in the investigation of neurotoxicity and developmental neural toxicity caused by environmental pollutants. The study also explores the culturing techniques employed for these cell lines and provides an overview of the standardized assays used to assess various biological endpoints. The environmental pollutants involved include a variety of organic compounds, heavy metals, and microplastics. The utilization of cell lines derived from human sources holds significant significance in elucidating the neurotoxic effects of environmental pollutants and the underlying mechanisms. Finally, we propose the possibility of improving the in vitro model of the human nervous system and the toxicity detection methods.

Mediating role of anxiety and impulsivity in the association between child maltreatment and lifetime non-suicidal self-injury with and without suicidal self-injury.

BACKGROUND: Child maltreatment can increase the risk of lifetime non-suicidal self-injury (NSSI) and suicidal self-injury (SSI), but there is limited knowledge regarding the differences of potentially psychological mechanisms between NSSI with and without SSI. METHODS: Participants, 3918 community-based Chinese young men aged 18-34 years in Chengdu, were included in this study. We investigated the association between depression, anxiety, psychosis, child maltreatment, adulthood traumatic events, impulsivity, alcohol dependence, drug abuse, and lifetime of NSSI among participants with and without SSI. Parallel mediation analysis was utilized to explore the mediators for the relation between child maltreatment and NSSI. RESULTS: The prevalence of lifetime NSSI was 6.1 % (95 % CI: 5.4 %-6.9 %) among young men. Anxiety and impulsivity partially mediated the effect of child maltreatment on NSSI either with (indirect effect: 51.2 %) or without SSI (indirect effect: 34.3 %). Depression was independently and significantly associated with only NSSI but not with NSSI+SSI. Alcohol dependence and psychosis were independently and significantly associated with NSSI+SSI and mediated the effect of child maltreatment on NSSI+SSI. LIMITATIONS: The cross-sectional survey data limits the robustness of the proof to the causal relationships. CONCLUSIONS: Anxiety and impulsivity are associated with NSSI either with or without SSI and partially mediate the effect of child maltreatment on NSSI. Depression is associated with only NSSI, while alcohol dependence and psychosis are only associated with NSSI+SSI. It could be crucial to improve treatment and recovery of alcohol dependence and psychosis for preventing young men engaged in NSSI from attempting SSI.

Application of dynamic coronary roadmap in coronary artery low-dose mode / 介入放射学杂志

Objective To clarify whether the use of dynamic coronary artery roadmap(DCR)technology in a low-dose mode with 7.5 frames per second during coronary intervention can further reduce the total radiation dose,fluoroscopy time,and contrast agent usage.Methods A total of 94 patients,who received coronary angiography at the Shanghai Tongji Hospital of China between July 2022 and December 2022,were enrolled in this study.The patients were randomly divided into DCR group(n=53)and control group(n=41).DCR technology was used in the DCR group to guide the performance of percutaneous coronary intervention(PCI),while low-dose mode coronary angiography was adopted in the control group.The total air kerma(AK),dose-area product(DAP),intraoperative fluoroscopy time,and contrast agent usage were compared between the two groups.Results In the DCR group AK was(597.9±222.8)mGy,which was significantly lower than(717.0±326.8)mGy in the control group(P=0.039);DAP was(33.2±13.3)Gycm2/s,which was also remarkably lower than(41.3±21.5)Gycm2/s in the control group(P=0.027).In the DCR group and the control group,the intraoperative fluoroscopy time was(9.8± 3.3)min and(12.1±4.3)min respectively(P＜0.01),and the contrast agent usage was(122.3±19.0)mL and(130.5± 28.5)mL respectively(P=0.116).Conclusion In a low-dose mode during coronary intervention,the use of DCR technology can further reduce radiation dose,fluoroscopy time,and contrast agent usage.(J Intervent Radiol,2024,33:236-239)