Selective Hydroboration of C-C Single Bonds without Transition-metal Catalysis.

Selective hydroboration of C-C single bonds presents a fundamental challenge in the chemical industry. Previously, only catalytic systems utilizing precious metals Ir and Rh, in conjunction with N- and P- ligands, could achieve this, ensuring bond cleavage and selectivity. In sharp contrast, we discovered an unprecedented and general transition-metal-free system for the hydroboration of C-C single bonds. This methodology is transition-metal and ligand-free and surpasses the transition-metal systems regarding chemo- and regioselectivities, substrate versatility, or yields. In addition, our system tolerates various functional groups such as Ar-X (X = halides), heterocyclic rings, ketones, esters, amides, nitro, nitriles, and C=C double bonds, which are typically susceptible to hydroboration in the presence of transition metals. As a result, a diverse range of γ-boronated amines with varied structures and functions has been readily obtained. Experimental mechanistic studies, density functional theory (DFT), and intrinsic bond orbital (IBO) calculations unveiled a hydroborane-promoted C-C bond cleavage and hydride-shift reaction pathway. The carbonyl group of the amide suppresses dehydrogenation between the free N-H and hydroborane. The lone pair on the nitrogen of the amide facilitates the cleavage of C-C bonds in cyclopropanes.

Synthesis of C(3) SCF3-Substituted Pyrrolidinoindoline by PIII/PV Redox Catalysis Using CF3SO2Cl as Electrophilic CF3S Reagent.

This work reports a method for the catalytic synthesis of C(3) SCF3-substituted pyrrolidinindoline using a small-ring organophosphorus-based catalyst and a hydrosilane reductant, with trifluoromethanesulfonyl chloride as the electrophilic SCF3 reagent. This method can drive the conversion of tryptamine to the C(3) SCF3-substituted pyrrolidine indoline. The readily available, inexpensive trifluoromethanesulfonyl chloride could be activated as an electrophilic SCF3 source by PIII/PV redox catalysis and could efficiently participate in the reaction of tryptamines, thus providing various substituted C(3) SCF3-substituted pyrrolidinoindoline in moderate to excellent yields. This presented strategy features a broad substrate scope, and the structure has value for in-depth research.

Polarization-insensitive multimode interference coupler on an x-cut thin-film lithium niobate platform.

Thin-film lithium niobate (TFLN) is a promising integrated photonics platform but currently lacks a polarization-insensitive multimode interference (MMI) coupler, a crucial component for polarization-related optical communication applications such as polarization management, polarization-division multiplexing, and polarization-insensitive modulation systems. This paper presents a novel, to the best of our knowledge, approach by rotating the MMI structure on an anisotropic x-cut TFLN at specific angles to compensate for the difference in the beat length between the two polarizations. A polarization-insensitive 1 × 2 MMI coupler is experimentally achieved with measured transmittances of -2.5 to -4 dB for both output ports and polarization modes in the wavelength range of 1520-1580 nm.

Single nucleotide polymorphisms in SEPALLATA 2 underlie fruit length variation in cucurbits.

Complete disruption of critical genes is generally accompanied by severe growth and developmental defects, which dramatically hinder its utilization in crop breeding. Identifying subtle changes, such as single nucleotide polymorphisms (SNPs), in critical genes that specifically modulate a favorable trait is a prerequisite to fulfill breeding potential. Here, we found two SNPs in the E-class floral organ identity gene cucumber (Cucumis sativus) SEPALLATA2 (CsSEP2) that specifically regulate fruit length. Haplotype (HAP) 1 (8G2667A) and HAP2 (8G2667T) exist in natural populations, whereas HAP3 (8A2667T) is induced by ethyl methanesulfonate mutagenesis. Phenotypic characterization of four near-isogenic lines and a mutant line showed that HAP2 fruits are significantly longer than those of HAP1, and those of HAP3 are 37.8% longer than HAP2 fruit. The increasing fruit length in HAP1-3 was caused by a decreasing inhibitory effect on CRABS CLAW (CsCRC) transcription (a reported positive regulator of fruit length), resultinged in enhanced cell expansion. Moreover, a 7638G/A-SNP in melon (Cucumis melo) CmSEP2 modulates fruit length in a natural melon population via the conserved SEP2-CRC module. Our findings provide a strategy for utilizing essential regulators with pleiotropic effects during crop breeding.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

Cross-modal group-relation optimization for visible-infrared person re-identification.

Visible-infrared person re-identification (VIPR) plays an important role in intelligent transportation systems. Modal discrepancies between visible and infrared images seriously confuse person appearance discrimination, e.g., the similarity of the same class of different modalities is lower than the similarity between different classes of the same modality. Worse still, the modal discrepancies and appearance discrepancies are coupled with each other. The prevailing practice is to disentangle modal and appearance discrepancies, but it usually requires complex decoupling networks. In this paper, rather than disentanglement, we propose to measure and optimize modal discrepancies. We explore a cross-modal group-relation (CMGR) to describe the relationship between the same group of people in two different modalities. The CMGR has great potential in modal invariance because it considers more stable groups rather than individuals, so it is a good measurement for modal discrepancies. Furthermore, we design a group-relation correlation (GRC) loss function based on Pearson correlations to optimize CMGR, which can be easily integrated with the learning of VIPR's appearance features. Consequently, our CMGR model serves as a pivotal constraint to minimize modal discrepancies, operating in a manner similar to a loss function. It is applied solely during the training phase, thereby obviating the need for any execution during the inference phase. Experimental results on two public datasets (i.e., RegDB and SYSU-MM01) demonstrate that our CMGR method is superior to state-of-the-art approaches. In particular, on the RegDB dataset, with the help of CMGR, the rank-1 identification rate has improved by more than 7% compared to the case of not using CMGR.

Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

DLX6-AS1 regulates odonto/osteogenic differentiation in dental pulp cells under the control of BMP9 via the miR-128-3p/MAPK14 axis: A laboratory investigation.

AIM: The regenerative capacity of dental pulp relies on the odonto/osteogenic differentiation of dental pulp cells (DPCs), but dynamic microenvironmental changes hinder the process. Bone morphogenetic protein 9 (BMP9) promotes differentiation of DPCs towards an odonto/osteogenic lineage, forming dentinal-like tissue. However, the molecular mechanism underlying its action remains unclear. This study investigates the role of DLX6 antisense RNA 1 (DLX6-AS1) in odonto/osteogenic differentiation induced by BMP9. METHODOLOGY: Custom RT2 profiler PCR array, quantitative Real-Time PCR (qRT-PCR) and western blots were used to investigate the expression pattern of DLX6-AS1 and its potential signal axis. Osteogenic ability was evaluated using alkaline phosphatase and alizarin red S staining. Interactions between lncRNA and miRNA, as well as miRNA and mRNA, were predicted through bioinformatic assays, which were subsequently validated via RNA immunoprecipitation and dual luciferase reporter assays. Student's t-test or one-way ANOVA with post hoc Tukey HSD tests were employed for data analysis, with a p-value of less than .05 considered statistically significant. RESULTS: DLX6-AS1 was upregulated upon BMP9 overexpression in DPCs, thereby promoting odonto/osteogenic differentiation. Additionally, miR-128-3p participated in BMP9-induced odonto/osteogenic differentiation by interacting with the downstream signal MAPK14. Modifying the expression of miR-128-3p and transfecting pcMAPK14/siMAPK14 had a rescue impact on odonto/osteogenic differentiation downstream of DLX6-AS1. Lastly, miR-128-3p directly interacted with both MAPK14 and DLX6-AS1. CONCLUSIONS: DLX6-AS1 could regulate the odonto/osteogenic differentiation of DPCs under the control of BMP9 through the miR-128-3p/MAPK14 axis.

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009-2014.

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV-1, and HSV-2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26-1.70; OR 1.09, 95% CI 1.05-1.13; OR 1.06, 95% CI 1.01 - 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29-1.77; OR 1.08, 95% CI 1.04-1.12; OR 1.05, 95% CI 1.01-1.10, respectively) after adjusting all relevant co-factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV-1 infection, while the relationship between HSV-2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Clinical data-based modeling of IVF live birth outcome and its application.

BACKGROUND: The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. METHODS: The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. RESULTS: Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO. CONCLUSIONS: The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.

Class-Irrelevant Feature Removal for Few-Shot Image Classification.

Most existing few-shot image classification methods employ global pooling to aggregate class-relevant local features in a data-drive manner. Due to the difficulty and inaccuracy in locating class-relevant regions in complex scenarios, as well as the large semantic diversity of local features, the class-irrelevant information could reduce the robustness of the representations obtained by performing global pooling. Meanwhile, the scarcity of labeled images exacerbates the difficulties of data-hungry deep models in identifying class-relevant regions. These issues severely limit deep models' few-shot learning ability. In this work, we propose to remove the class-irrelevant information by making local features class relevant, thus bypassing the big challenge of identifying which local features are class irrelevant. The resulting class-irrelevant feature removal (CIFR) method consists of three phases. First, we employ the masked image modeling strategy to build an understanding of images' internal structures that generalizes well. Second, we design a semantic-complementary feature propagation module to make local features class relevant. Third, we introduce a weighted dense-connected similarity measure, based on which a loss function is raised to fine-tune the entire pipeline, with the aim of further enhancing the semantic consistency of the class-relevant local features. Visualization results show that CIFR achieves the removal of class-irrelevant information by making local features related to classes. Comparison results on four benchmark datasets indicate that CIFR yields very promising performance.

Integrating plasma proteomics with genome-wide association data to identify novel drug targets for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn's disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD).

Barley polysaccharides inhibit colorectal cancer by two relatively independent pathways.

Colorectal cancer is one of the most common types of cancer worldwide that can lead to serious injury and death. Although polysaccharides are widely recognized as having antitumor activity, there has been little research on the role of barley polysaccharides (BP)1 in colorectal cancer. The results of our research suggest that BP (300 mg/kg) had a significant inhibitory effect on colorectal cancer, and this effect was achieved through two pathways. First, BP can directly promote the secretion of protective metabolites like 5-(4-Hydroxyphenyl)-5-phenylimidazolidine-2,4-dione and 2,3-Bis(4-hydroxyphenyl)propionitrile thereby inhibiting the cancer pathways such as ERK, PI3K, WNT, JAK-STAT, Calcium, and Cell cycle cancer pathways to alleviate inflammation. Second, BP also can enrich beneficial intestinal bacteria such as Colidextribacter, Bilophila, and UCG-003 improve the intestinal barrier, promote the production of beneficial metabolites such as 5,8-Epoxy-5,8-dihydro-3-hydroxy-8'-apo-b,y-carotenal and L-Glutamic acid, and thus inhibit cancer pathways such as ERK, PI3K, Nuclear receptor, Cell cycle, Apoptosis and TGF-ß. In conclusion, our findings suggest for the first time that BP can alleviate colorectal cancer by two relatively independent pathways: direct action and indirect action via the gut microbiota on both colon tumor cells and microbiota.

Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway.

Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients' tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial-mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.

Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice.

Male patients who undergo prepubertal chemotherapy face the dual problems of fertility preservation in adulthood, including low testosterone, hypersexual function, and infertility. Humanin, as a small polypeptide coded within the mitochondrial DNA, with the mitochondrial short open reading frame named MOTS-c, both was believed to regulate mitochondrial homeostasis, be anti-inflammatory, improve metabolism, anti-apoptosis, and multiple pharmacological effects. However, there exists little evidence that reported Humanin and MOTS-c 's effects on moderating male spermatogenic function of patients after prepubertal chemotherapy. Here, we found that in vivo, mitochondrial polypeptides Humanin analog (HNG) and MOTS-c efficaciously protected the testicular spermatogenic function from reproductive injury. Moreover, transcriptomic sequencing analysis was performed to verify the differentially expressed genes such as Piwil2, AGT (angiotensinogen), and PTGDS (glycoprotein prostaglandin D2 synthase), which are related to the regulation of male reproductive function of male mice induced by prepubertal chemotherapy. Collectively, our data revealed that both Humanin analogs HNG and MOTS-c are the feasible approaches attached to the protective effect on the male reproductive function damaged by prepubertal chemotherapy.

Identification of novel drug targets for multiple sclerosis by integrating plasma genetics and proteomes.

BACKGROUND: Genome-wide association studies (GWAS) have revealed numerous loci associated with multiple sclerosis (MS). However, the challenge lies in deciphering the mechanisms by which these loci influence the target traits. Here, we employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for MS. METHODS: We systematically integrated MS GWAS data (N = 115,803) with human plasma proteome data (N = 7213) and conducted proteome-wide association studies (PWAS) to identify MS-associated pathogenic proteins. Following this, we employed Mendelian randomization and Bayesian colocalization analyses to verify the causal relationship between these significant plasma proteins and MS. Lastly, we utilized the Drug-Gene Interaction Database (DGIdb) to identify potential drug targets for MS. RESULTS: The PWAS identified 25 statistically significant cis-regulated plasma proteins associated with MS at a false discovery rate of P < 0.05. Further analysis revealed that the abundance of 7 of these proteins (PLEK, TNXB, CASP3, CD59, CR1, TAPBPL, ATXN3) was causally related to the incidence of MS. Our findings indicated that genetically predicted higher levels of TNXB and CD59 were associated with a lower risk of MS, whereas higher levels of PLEK, CASP3, CR1, TAPBPL, and ATXN3 were associated with an increased risk of MS. Three plasma proteins (PLEK, CR1, CD59) were validated by colocalization analysis. Among these, CR1 was prioritized as a target for Eculizumab due to its significant association with MS risk. Additionally, PLEK, CR1, and CD59 were identified as druggable target genes. CONCLUSIONS: Our proteomic analysis has identified PLEK, CR1, and CD59 as potential drug targets for MS treatment. Developing pharmacological inducers or inhibitors for these proteins could pave the way for new therapeutic approaches, potentially improving outcomes for MS patients.

Global prevalence of obesity in patients with psoriasis: An analysis in the past two decades.

BACKGROUND: Obesity is the risk factor for psoriasis. Therefore, we conducted a comprehensive review and meta-analysis to determine the prevalence of obesity in patients with psoriasis. METHODS: We examined four databases from their inception to October 2023 and used the Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale to assess the quality of observational studies. Data analysis was conducted by R language. Meta-regression, sensitivity and subgroup analyses were used to evaluate inter-study heterogeneity. Egger's test and funnel plots were used to evaluate publication bias. RESULTS: The global prevalence of psoriasis and obesity comorbidity was 25% (95% confidence interval [CI]: 0.21-0.30). Furthermore, the co-morbidity rate was 18% (95% CI: 0.11-0.24) in children and adolescents, and 35% (95% CI: 0.30-0.39) in adults. The gender-specific prevalence rates were 23% (95% CI: 0.16-0.32) in men and 38% (95% CI: 0.20-0.61) in women. Africa had the highest prevalence (60%, 95% CI: 0.21-0.99), followed by Asia (40%, 95% CI: 0.28-0.51), while Europe and North America had similar prevalence rates at 34% (95% CI: 0.27-0.41) and 31% (95% CI: 0.27-0.38), respectively. Regarding psoriasis severity, obesity prevalence was higher in moderate psoriasis (36%, 95% CI: 0.20-0.64) and lower in mild psoriasis (27%, 95% CI: 0.16-0.46). The prevalence of obesity in the patients with severe psoriasis was 30% (95% CI: 0.20-0.45). CONCLUSION: This study underscores the importance of identifying and treating obesity in patients with psoriasis to mitigate disease progression. However, more high-quality observational studies are required to elucidate their global prevalence and comorbid associations.

Engineered Mesenchymal Stromal Cell Exosomes-Loaded Microneedles Improve Corneal Healing after Chemical Injury.

Corneal alkali burns represent a prevalent ophthalmic emergency with the potential to induce blindness. The main contributing mechanisms include excessive inflammation and delayed wound healing. Existing clinical therapies have limitations, promoting the exploration of alternative methods that offer improved efficacy and reduced side effects. Adipose-derived stem cell-exosome (ADSC-Exo) has the potential to sustain immune homeostasis and facilitate tissue regeneration. Nevertheless, natural ADSC-Exo lacks disease specificity and exhibits limited bioavailability on the ocular surface. In this study, we conjugated antitumor necrosis factor-α antibodies (aT) to the surface of ADSC-Exo using matrix metalloproteinase-cleavable peptide chains to create engineered aT-Exo with synergistic effects. In both in vivo and in vitro assessments, aT-Exo demonstrated superior efficacy in mitigating corneal injuries compared to aT alone, unmodified exosomes, or aT simply mixed with exosomes. The cleavable conjugation of aT-Exo notably enhanced wound healing and alleviated inflammation more effectively. Simultaneously, we developed poly(vinyl alcohol) microneedles (MNs) for precise and sustained exosome delivery. The in vivo results showcased the superior therapeutic efficiency of MNs compared with conventional topical administration and subconjunctival injection. Therefore, the bioactive nanodrugs-loaded MNs treatment presents a promising strategy for addressing ocular surface diseases.