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Abstract To investigate the knowledge, attitude, and practice (KAP) of photoaging in the Chinese population. This web-based cross-sectional study was conducted between January 2023 and March 2023 among the Chinese population aged 18–80 years old. Participants’ knowledge, attitude, and practice toward photoaging were collected through a self-administered questionnaire. A total of 830 questionnaires were collected, with 826 valid questionnaires and an efficiency rate of 99.52%. There were 274 (33.17%) males and 532 (64.41%) aged 31–51 years old. The average knowledge, attitude, and practice scores were 7 (4, 9) (possible range 0–12), 31.5 (28, 34) (possible range 8–40), and 33 (24, 42) (possible range 11–55), respectively, indicating poor knowledge, good attitude, and moderate practice. Spearman correlation analysis showed that knowledge was negatively correlated with attitude (r = − 0.111, P

BackgroundCell energy metabolism controls the activation and function of dendritic cells (DCs). Inflammatory dendritic epidermal cells (IDECs) in skin lesions of atopic dermatitis (AD) express high-affinity IgE receptor (FcϵRI) and toll-like receptor 2 (TLR2), which mediate the generation and maintenance of inflammation. However, cellular energy metabolism and effector function of IDECs mediated by FcϵRI and TLR2 have not been fully elucidated.MethodsIDECs in vitro were treated with TLR2 agonist Pam3CSK4 and anti-IgE alone or in combination for 24 h. Further, we analyzed the expression of cell surface activation markers, production of inflammatory factors, and cellular energy metabolism profiles of IDECs by using flow cytometry, multiplex assay, RNA sequencing, targeted energy metabolism, and seahorse assays.ResultsCompared to the unstimulated or anti-IgE groups, Pam3CSK4 alone or combined with anti-IgE groups significantly increased the expression of CD80, CD83, and CD86 on IDECs, but did not affect the expression of the above markers in the anti-IgE group. The release of inflammatory cytokines increased in the Pam3CSK4 alone or combined with anti-IgE groups, while there was a weak increasing trend in the anti-IgE group. The glycolysis/gluconeogenesis pathway of carbon metabolism was affected in all treatment groups. Furthermore, compared to the control group, we found a decrease in pyruvic acid, upregulation of PFKM, downregulation of FBP1, and increase in extracellular lactate, glycolysis rate, and glycolysis capacity after all treatments, while there was no difference between each treatment group. However, there was no difference in glycolytic reserve and mitochondrial basic and maximum respiration among all groups.ConclusionOur results indicate that glycolysis of IDECs may be activated through FcϵRI and TLR2 to upregulate inflammatory factors, suggesting that danger signals from bacteria or allergens might evoke an inflammatory response from AD through the glycolysis pathway.

Breast cancer (BC) is the prevailing malignancy among women, with HER2 overexpression observed in 20–30 % of all BC, thereby serving as a prognostic indicator for unfavorable outcomes in affected individuals. There is a necessity to establish innovative treatment protocols to expand the therapeutic alternatives accessible for managing HER2-positive BC. In this study, we report a case of HER2-positive BC that was managed in our department using a combination of three targeted drugs (Trastuzumab, Pertuzumab and Pyrotinib) along with chemotherapy. The treatment resulted in a pathological complete response (pCR) and was observed to be well-tolerated, without any significant adverse reactions. Hence, the combination of Pyrotinib and Dual HER2 blockade treatment shows promise as a neoadjuvant therapy for locally advanced HER2-positive BC to achieve a pCR in surgery. Nevertheless, this conclusion necessitates additional validation via meticulously designed clinical research investigations encompassing larger patient populations.

Vaginitis, characterized by pathogenic invasion and a deficiency in beneficial lactobacilli, has recognized lactobacilli supplementation as a novel therapeutic strategy. However, due to individual differences in vaginal microbiota, identifying universally effective Lactobacillus strains is challenging. Traditional methodologies for probiotic selection, which heavily depend on extensive in vitro experiments, are both time-intensive and laborious. The aim of this study was to pinpoint possible vaginal probiotic candidates based on whole-genome screening. We sequenced the genomes of 98 previously isolated Lactobacillus strains, annotating their genes involved in probiotic metabolite biosynthesis, adherence, acid/bile tolerance, and antibiotic resistance. A scoring system was used to assess the strains based on their genomic profiles. The highest-scoring strains underwent further in vitro evaluation. Consequently, two strains, Lactobacillus crispatus LG55-27 and Lactobacillus gasseri TM13-16, displayed an outstanding ability to produce d-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity against Gardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa compared to reference Lactobacillus strains. Their resilience to acid and bile environments highlights the potential for oral supplementation. Oral and vaginal administration of these two strains were tested in a bacterial vaginosis (BV) rat model at various doses. Results indicated that combined vaginal administration of these strains at 1 × 106 CFU/day significantly mitigated BV in rats. This research offers a probiotic dosage guideline for vaginitis therapy, underscoring an efficient screening process for probiotics using genome sequencing, in vitro testing, and in vivo BV model experimentation.

Abstract Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.

Background: Contrast retention (CR) is an important predictor of left atrial appendage thrombus (LAAT) and stroke in patients with non-valvular atrial fibrillation (AF). We sought to explore the underlying mechanisms of CR using computational fluid dynamic (CFD) simulations. Methods: A total of 12 patients with AF who underwent both cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before left atrial appendage occlusion (LAAO) were included in the study. The patients were allocated into the CR group or non-CR group based on left atrial appendage (LAA) angiography. Patient-specific models were reconstructed to evaluate time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP). Additionally, the incidence of thrombosis was predicted using residence time (RT) at different time-points. Results: TAWSS was lower [median (Interquartile Range) 0.27 (0.19–0.47) vs 1.35 (0.92–1.79), p

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

Abstract Cyclic peptides are poised to target historically difficult to drug intracellular protein–protein interactions, however, their general cell impermeability poses a challenge for characterizing function. Recent advances in microfluidics have enabled permeabilization of the cytoplasmic membrane by physical cell deformation (i.e., mechanoporation), resulting in intracellular delivery of impermeable macromolecules in vector‐ and electrophoretic‐free approaches. However, the number of payloads (e.g., peptides) and/or concentrations delivered via microfluidic mechanoporation is limited by having to pre‐mix cells and payloads, a manually intensive process. In this work, we show that cells are momentarily permeable (t1/2 = 1.1–2.8 min) after microfluidic vortex shedding (μVS) and that lower molecular weight macromolecules can be cytosolically delivered upon immediate exposure after cells are processed/permeabilized. To increase the ability to screen peptides, we built a system, dispensing‐microfluidic vortex shedding (DμVS), that integrates a μVS chip with inline microplate‐based dispensing. To do so, we synced an electronic pressure regulator, flow sensor, on/off dispense valve, and an x‐y motion platform in a software‐driven feedback loop. Using this system, we were able to deliver low microliter‐scale volumes of transiently mechanoporated cells to hundreds of wells on microtiter plates in just several minutes (e.g., 96‐well plate filled in

Considering the current limitations of intelligent interactive in electronic integration and luminescent modes, this paper proposes a novel fabrication method for pressure-sensing POF fabrics with a non-direct-contact conductive system. In this system, conductive materials are concealed in the fabric structure to avoid direct contact with the human body. It was enabled by integrating layered weave structure, POFs, conductive yarns, and fabric patches within the fabric. Laser engraving was also applied on the fabric surface to achieve intricate pattern design. Experimental tests were conducted on sensing and luminescent properties of this POF fabric. The circuit module and software were developed to support the interactive function. The potential application of this fabric in the interior components of intelligent cockpits was envisioned. The research results show that the POF fabric integrated with conductive yarns and conductive fabric patches has good pressure sensitivity, enabling control of the fabric’s luminescent color by pressing the fabric surface. The non-direct-contact conductive system developed in this study offers the advantage of electrical signal stability by avoiding interference from human body resistance and grounding conditions. The development of this type of interactive luminescent textile holds promising prospects for application and development in various fields, including intelligent cockpits.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

Abstract Background Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state, and it may have detrimental effects on female reproduction and fertility. Oleic acid induces lipid accumulation in bovine granulosa cells, which leads to a foam cell-like morphology and reduced steroidogenesis. However, why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear. This study focused on oleic acid’s effects on lipid type and steroidogenesis. Results Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level. Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro. In addition, oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2, but down-regulated the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2, as well as steroidogenesis-related genes, including cytochrome P450 family 11 subfamily A member 1, cytochrome P450 family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels. An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice, which resulted in lower estradiol levels than in control-fed mice. Compared with the control, decreases in estrus days and the numbers of antral follicles and corpora lutea, as well as an increase in the numbers of the atretic follicles, were found in the oleic acid-fed female mice. Conclusions Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells, and led to a decrease in steroidogenesis. These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.

Abstract Background Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE Methods Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE. Results Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). Conclusions The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.

Gastrointestinal (GI) disorders are very common among children with cerebral palsy. Gut microbiota has been confirmed to maintain normal GI physiological function and further contributed to cerebral palsy through the gut-brain axis. Our study was to investigate the effect of dietary fiber combined with probiotics on functional constipated children with cerebral palsy. In total, 35 patient children were enrolled and divided into general diet group (n = 14) and liquid diet group (n = 21). All the participants received Compound Dietary Fiber (CDF) for 1 month and lactic acid-producing and butyric acid-producing probiotics for 6 months. After a 1-month intervention, the frequency of spontaneous and manual defecation, and Bristol score were all significantly improved (P < 0.001). The α-diversity of the gut microbiota was significantly increased after a 1-month intervention (P < 0.05), with a higher abundance of butyric acid-producing bacteria and a lower abundance of opportunistic pathogens (P < 0.05, FDR < 0.05). However, the impersistent effect of the 6-month intervention suggested the insufficient impact of intaking probiotics alone and the short duration of CDF intervention. Moreover, although the intervention had affected the constipation symptoms equally in cerebral palsy children with a general diet and liquid diet, the general diet group showed a greater and more durable change in gut microbiota and clinical phenotypes after intervention than the liquid diet group, which indicated that longer intervention time should be considered for liquid diet children. This study not only illustrated that supplementation of dietary fiber combined with probiotics can improve functional constipation in children with cerebral palsy, but also provides guidance for optimal intervention strategy for future studies, which will further benefit cerebral palsy children.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=46902, identifier: ChiCTR1900028257.

Abstract Background There is still a certain gap between the effective implementation and requirements of sepsis bundle. Our aim is to establish the clinical nursing pathway of the cluster treatment of septic shock in the Intensive Care Unit and promote effective implementation of the cluster treatment of septic shock. Methods By means of evidence-based method, quality control index requirements and on-site investigation, the implementation process of clinical nursing pathway of the cluster treatment within 6 h of diagnosis of septic shock was established. Results After the implementation of clinical nursing pathway, the completion rate of septic shock cluster treatment was 81.4% (66.4%) in 1 h, 89.4% (77.0%) in 3 h, 95.5% (82.3%) in 6 h (P

Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology. The epigenetic regulation of N6-methyladenosine (m6A) modification in immunity is emerging. However, few studies have focused on SLE and m6A immune regulation. In this study, we aimed to explore a potential integrated model of m6A immunity in SLE. The models were constructed based on RNA-seq data of SLE. A consensus clustering algorithm was applied to reveal the m6A-immune signature using principal component analysis (PCA). Univariate and multivariate Cox regression analyses and Kaplan–Meier analysis were used to evaluate diagnostic differences between groups. The effects of m6A immune-related characteristics were investigated, including risk evaluation of m6A immune phenotype-related characteristics, immune cell infiltration profiles, diagnostic value, and enrichment pathways. CIBERSORT, ESTIMATE, and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the relative immune cell infiltrations (ICIs) of the samples. Conventional bioinformatics methods were used to identify key m6A regulators, pathways, gene modules, and the coexpression network of SLE. In summary, our study revealed that IGFBP3 (as a key m6A regulator) and two pivotal immune genes (CD14 and IDO1) may aid in the diagnosis and treatment of SLE. The potential integrated models of m6A immunity that we developed could guide clinical management and may contribute to the development of personalized immunotherapy strategies.

Objective: This study aimed to explore the influence of gratitude on the meaning of life of college students and the mediating effect of family function and peer relationships.Methods: A total of 1,049 college students (mean age: 18.59 ± 0.96 years) were investigated by gratitude scale, family function scale, peer relationship questionnaire, and meaning of life scale.Results: (1) Gratitude was positively correlated with meaning existence (r = 0.39, P < 0.05), meaning seeking (r = 0.23, P < 0.05), and peer relationship (r = 0.32, P < 0.05); meanwhile, it is also positively correlated with family function (r = 0.34, P < 0.05); (2) family function partially mediates the relationship between gratitude and meaning of life. Similarly, peer relationship partially mediates the relationship between gratitude and meaning of life.Conclusion: The mediating model showed that grateful individuals can better sense the meaning of life by perceiving good family function and good peer relationships.

This study aimed to investigate the effect and potential modulation mechanism of lnc-SLC4A1-1 on breast cancer (BC) carcinogenesis. The expression of lnc-SLC4A1-1 in tissue and serum samples from BC patients, as well as BC cell lines, was detected by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Next, the expression of lnc-SLC4A1-1 was silenced or upregulated in BC cells, then cell proliferation, apoptosis, migration and invasion were detected using MTT, flow cytometry analysis and Transwell assay. Meanwhile, the expression of apoptosis-related proteins and epithelial-mesenchymal transition-related proteins were detected by western blotting. Furthermore, potential mechanism of lnc-SLC4A1-1 was explored by chromatin immunoprecipitation and RNA immunoprecipitation assays. CXCL8 was overexpressed to evaluate the relationship between lnc-SLC4A1-1 and CXCL8. Lnc-SLC4A1-1 was significantly up-regulated in BC tissue, serum samples and cell lines. In BC cells, lnc-SLC4A1-1 knockdown promoted cell apoptosis and suppressed cell proliferation, migration and invasion. Furthermore, lnc-SLC4A1-1 is transcriptionally activated by H3K27 acetylation, and lnc-SLC4A1-1 interacted with transcription factor (NF)-κB p65, thereby regulating CXCL8 expression. Meanwhile, CXCL8 overexpression partly reversed the effects of lnc-SLC4A1-1 knockdown on cell viability, apoptosis, migration and invasion in BC cells. Lnc-SLC4A1-1 could promote the development of BC by regulating NF-κB/CXCL8.HighlightsLnc-SLC4A1-1 was overexpressed in BC tissues, blood and cell lines.Lnc-SLC4A1-1 was transcriptionally activated by H3K27 acetylation.Lnc-SLC4A1-1 interacted with NF-κB to promote CXCL8 expression.Lnc-SLC4A1-1 could promote the development of BC.

The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.

PurposeSystemic lupus erythematosus (SLE) is a serious autoimmune disease. Its molecular pathogenesis, especially the long non-coding RNA (lncRNA) function, remains unclear. We want to investigate the lncRNA dysregulation profile and their molecular mechanisms in SLE.MethodsIn this study, we analyzed the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PBMCs) from SLE patients and two published transcriptome datasets to explore lncRNA profiles. The differentially expressed lncRNAs were confirmed by quantitative real-time PCR in another set of female patients. We constructed the lncRNA-mRNA regulatory networks by performing weighted gene co-expression network analysis (WGCNA). Dysregulated lncRNA AC007278.2 was repressed by short hairpin RNA (shRNA) in Jurkat cells. Dual-luciferase reporter gene assay was performed to investigate the regulatory mechanism of AC007278.2 on target gene CCR7.ResultsWe observed dominant up-regulation of transcripts, including mRNAs and lncRNAs, in SLE patients. By WGCNA method, we identified three modules that were highly related to SLE. We then focused on one lncRNA, AC007278.2, with a T-helper 1 lineage-specific expression pattern. We observed consistently higher AC007278.2 expression in SLE patients. Co-expression network revealed that AC007278.2 participated in the innate immune response and inflammatory bowel disease pathways. By knocking down AC007278.2 expression, we found that AC007278.2 could regulate the expression of inflammatory and cytokine stimulus response-related genes, including CCR7, AZU1, and TNIP3. AC007278.2 inhibits the functional CCR7 promoter to repress its transcription, thereby regulating autoimmunity and follicular T-helper cell differentiation.ConclusionIn summary, our study indicated the important regulatory role of lncRNAs in SLE. AC007278.2 may be treated as a novel biomarker for SLE diagnosis and treatment.

Disconnects between farming and urban systems are widely seen as impairing the resilience of biobased production systems (BBPSs). However, the institutional mechanisms that underlie these resilience problems are not well understood. In this explorative paper, which integrates elements from institutional and resilience theory, we develop a framework to analyze how institutionally shaped patterns of connects and disconnects affect the resilience of BBPs along the dimensions of robustness, adaptability, and transformability. This framework is applied to the historical case of pig livestock intensification in the Netherlands from 1870 to 2017. The case shows that institutions, successfully established in earlier periods, shape connects and disconnects in subsequent periods, thereby enabling and constraining resilience. A combination of perturbations, institutional layering, and shifts in ideational power is an important institutional mechanism for resilience. We conclude that building resilience requires a variety of reconnecting institutions and refraining from a focus on local reconnects or certification only.

BACKGROUND: Emerging evidence shows that anti-inflammatory strategies targeting inflammatory monocyte subset could reduce excessive inflammation and improve cardiovascular outcomes. Functional expression of voltage-gated sodium channels (VGSCs) have been demonstrated in monocytes and macrophages. We hypothesized that mononuclear phagocyte VGSCs are a target for monocyte/macrophage phenotypic switch, and liposome mediated inhibition of mononuclear phagocyte VGSC may attenuate myocardial ischemia/reperfusion (I/R) injury and improve post-infarction left ventricular remodeling. METHODOLOGY/PRINCIPAL FINDINGS: Thin film dispersion method was used to prepare phenytoin (PHT, a non-selective VGSC inhibitor) entrapped liposomes. Pharmacokinetic study revealed that the distribution and elimination half-life of PHT entrapped liposomes were shorter than those of free PHT, indicating a rapid uptake by mononuclear phagocytes after intravenous injection. In rat peritoneal macrophages, several VGSC α subunits (NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7, NaVX, Scn1b, Scn3b and Scn4b) and β subunits were expressed at mRNA level, and PHT could suppress lipopolysaccharide induced M1 polarization (decreased TNF-α and CCL5 expression) and facilitate interleukin-4 induced M2 polarization (increased Arg1 and TGF-β1 expression). In vivo study using rat model of myocardial I/R injury, demonstrated that PHT entrapped liposome could partially suppress I/R injury induced CD43+ inflammatory monocyte expansion, along with decreased infarct size and left ventricular fibrosis. Transthoracic echocardiography and invasive hemodynamic analysis revealed that PHT entrapped liposome treatment could attenuate left ventricular structural and functional remodeling, as shown by increased ejection fraction, reduced end-systolic and end-diastolic volume, as well as an amelioration of left ventricular systolic (+dP/dt max) and diastolic (-dP/dt min) functions. CONCLUSIONS/SIGNIFICANCE: Our work for the first time demonstrates the therapeutic potential of VGSC antagonism via liposome mediated monocyte/macrophage targeting in acute phase after myocardial I/R injury. These results suggest that VGSCs in mononuclear phagocyte system might be a novel target for immunomodulation and treatment of myocardial I/R injury.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Abstract Background The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle. Methods A retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group. Results For POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462–1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340–1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190–0.892, P = 0.024; aOR 0.358, 95% CI 0.155–0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI .624–0.922, P = 0.006 and OR 0.751, 95% CI 0.605–0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190–0.892, P = 0.024 and OR 0.367, 95% CI 0.161–0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2. Conclusions The findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients.

BackgroundMany smartphone apps designed to assist individuals in managing their weight are accessible, but the assessment of app quality and features has predominantly taken place in Western countries. Nevertheless, there is a scarcity of research evaluating weight management apps in China, which highlights the need for further investigation in this area. ObjectiveThis study aims to conduct a comprehensive search for the most popular commercial Chinese smartphone apps focused on weight management and assess their quality, behavior change techniques (BCTs), and content-related features using appropriate evaluation scales. Additionally, the study sought to investigate the associations between the quality of various domains within weight management apps and the number of incorporated BCTs and app features. MethodsIn April 2023, data on weight management apps from the iOS and Android app stores were downloaded from the Qimai Data platform. Subsequently, a total of 35 weight management apps were subjected to screening and analysis by 2 researchers. The features and quality of the apps were independently assessed by 6 professionals specializing in nutrition management and health behavioral change using the Mobile Application Rating Scale (MARS). Two registered dietitians, who had experience in app development and coding BCTs, applied the established 26-item BCT taxonomy to verify the presence of BCTs. Mean (SD) scores and their distributions were calculated for each section and item. Spearman correlations were used to assess the relationship between an app’s quality and its technical features, as well as the number of incorporated BCTs. ResultsThe data set included a total of 35 apps, with 8 available in the Android Store, 10 in the Apple Store, and 17 in both. The overall quality, with a mean MARS score of 3.44 (SD 0.44), showed that functionality was the highest scoring domain (mean 4.18, SD 0.37), followed by aesthetics (mean 3.43, SD 0.42), engagement (mean 3.26, SD 0.64), and information (mean 2.91, SD 0.52), which had the lowest score. The mean number of BCTs in the analyzed apps was 9.17 (range 2-18 BCTs/app). The most common BCTs were “prompt review of behavioral goals” and “provide instruction,” present in 31 apps (89%). This was followed by “prompt self-monitoring of behavior” in 30 apps (86%), “prompt specific goal setting” in 29 apps (83%), and “provide feedback on performance” in 27 apps (77%). The most prevalent features in the analyzed apps were the need for web access (35/35, 100%), monitoring/tracking (30/35, 86%), goal setting (29/35, 83%), and sending alerts (28/35, 80%). The study also revealed strong positive correlations among the number of BCTs incorporated, app quality, and app features. This suggests that apps with a higher number of BCTs tend to have better overall quality and more features. ConclusionsThe study found that the overall quality of weight management apps in China is moderate, with a particular weakness in the quality of information provided. The most prevalent BCTs in these apps were reviewing behavioral goals, providing guidance, self-monitoring of behavior, goal setting, and offering performance feedback. The most common features were the need for web access, monitoring and tracking, goal setting, and sending alerts. Notably, higher-quality weight management apps in China tended to incorporate more BCTs and features. These findings can be valuable for developers looking to improve weight management apps and enhance their potential to drive behavioral change in weight management.

Backgroundrs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined.MethodsThree-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns.ResultsGenerally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P

Pheochromocytomas have been shown to impair glucose tolerance and, rarely, to precipitate overt diabetes mellitus. We report here a case of a large pheochromocytoma in a woman with a recent diagnosis of diabetes mellitus that proved difficult to control despite high-dose insulin therapy who had complete resolution of her hyperglycemia following adrenalectomy. Her dramatic presentation demonstrates the need to consider this etiology in patients with new-onset insulin resistance and hypertension. Keywords: Pheochromocytoma, Insulin resistance, Impaired glucose tolerance, Diabetes mellitus

BackgroundFluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database.MethodsA retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDA-recommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher’s exact test.ResultsThe study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65.ConclusionFluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics.

Abstract A fluorescent porous organic polymer (FPOP) with strong fluorescence and tunable emission colors, was synthesized through a simple cost-effective method via Scholl coupling reaction. Experiments proved the stability and excellent detection and adsorption ability, and microporous nature of the material. Luminescence of FPOP was quenched when addition of nitroaromatic compounds. The properties along with large-scale and low-cost preparation make these FPOP potential candidates for fluorescence detection of nitroaromatic compounds. Additionally, FPOP shows higher adsorption capacity and rate than other reported adsorbents, and has the possibility of being an effective adsorbent for industrial usage. Moreover, a fluorescent test paper was further developed and is found to be sensitive to 10–8 M level, complete with a rapid response time and visual detection. This newly developed strategy may open up an avenue for exploring porous polymers, particularly those with a strong fluorescence, for the large-scale fabrication of FPOP for various advanced applications.

Objective: To investigate the current practice of extracorporeal cardiopulmonary resuscitation (ECPR) for Chinese cardiac arrest patients after the publication of 2015 American Heart Association guidelines for cardiopulmonary resuscitation. Methods: A questionnaire was distributed to healthcare providers of emergency departments (EDs) and/or Intensive Care Units (ICUs) across 52 hospitals in China from August to November 2016. Data collection ended in February 2017. The questionnaire included three parts: (1) characteristics of the departments and the respondents; (2) knowledge about ECPR; (3) practice of ECPR in cardiac arrest patients (case volume, inclusion/exclusion criteria, ECPR procedure). The characteristics of the departments/hospitals were only answered by the head of the department. Results: A total of 1 952 (86.8%) respondents fulfilled the survey. Only 2.5% of the respondents from 3 of 52 hospitals performed ECPR. Among the three hospitals, the case number of ECPR were ≤5 per year and none of them had written ECPR procedures. Only one hospital had formal inclusion/exclusion criteria. The inclusion criteria included age between 18 to 60 years, suspected cardiogenic cardiac arrest, beginning of cardiopulmonary resuscitation 10 min. The top three reasons for the nonuse of ECPR were unknown fields (31.2%), potential ECMO-related side effects (26.9%) and cost (18.7%). Conclusions: ECPR for cardiac arrest patients are not well understood by healthcare providers in the emergency department or ICUs and its application is still in the early stage in China. Educational training and other interventions are needed to promote the clinical practice.

The proteolytic activity of Furin responsible for processing full length Notch-1 (p300) plays a critical role in Notch signaling. The amplitude and duration of Notch activity can be regulated at various points in the pathway, but there has been no report regarding regulation of the Notch-1-Furin interaction, despite its importance. In the present study, we found that the Notch-1-Furin interaction is regulated by the non-receptor tyrosine kinase, c-Src. c-Src and Notch-1 are physically associated, and this association is responsible for Notch-1 processing and activation. We also found that growth factor TGF-α, an EGFR ligand, and PDGF-BB, a PDGFR ligand, induce the Notch-1-Furin interaction mediated by c-Src. Our results support three new and provocative conclusions: (1) The association between Notch-1 and Furin is a well-regulated process; (2) Extracellular growth factor signals regulate this interaction, which is mediated by c-Src; (3) There is cross-talk between the plasma growth factor receptor-c-Src and Notch pathways. Co-localization of Notch-1 and c-Src was confirmed in xenograft tumor tissues and in the tissues of pancreatic cancer patients. Our findings have implications for the mechanism by which the Notch and growth factor receptor-c-Src signaling pathways regulate carcinogenesis and cancer cell growth.