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OBJECTIVE: Breast cancer (BC) is one of the primary causes of tumor-related female mortalities. Although in recent years, we have made great progress in the systemic therapy and earlier diagnosis for BC patients, recurrence or distant metastasis remains leading obstacles for the successful therapy of BC. Therefore, a comprehensive understanding of the molecular mechanism underlying the progression may be crucial in developing an effective strategy against BC. The current research aimed to explore the expressions, functions and molecular mechanism of microRNA-491 (miR-491) in BC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of miR-491 expression in 52 pairs of BC tissues and para-cancerous specimens, and the relation between miR-491 level and the clinical features of BC patient prognosis was analyzed. Transwell invasion and migration assays were conducted to determine whether miR-491 had effects on the regulation of BC metastasis. Potential target genes of miR-491 were found out using TargetScan to explore the molecular functions of miR-491 in inhibiting breast cancer cell invasion and migration. To elucidate the mechanism of TPX2 in suppressing cell invasion and migration medicated by miR-491in breast cancer, we further transfected TPX2 siRNAs into MCF-7 cells to delete endogenous TPX2, along with the transfections with miR-491 inhibitor into MCF-7 cell lines. RESULTS: The findings demonstrated that miR-491 expressions were significantly decreased in BC tissues and cells. The miR-491 restoration suppressed the invasion and migration of BC cells. In addition, we identified the targeting protein for Xklp2 (TPX2) as a direct target of miR-491 in BC. The knockdown of TPX2 markedly reversed miR-491-medicated inhibition of cell invasion and migration in BC cell lines. CONCLUSIONS: In short, all the results suggested that miR-491 functioned as a tumor suppressor by targeting TPX2 in BC and the miR- 491 restoration may be an effective therapy for the BC treatment in the future. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Malytea Scurfpea fruit (MSF) on adhesion and migration of melanocyte. Methods: Human epidermal melanocytes were treated with MSF and examined for its adhesion to bovine serum fibronectin-coated culture plate and for its migration into micropore filters, which were then compared with those of untreated control. Results: Compared with the control, MSF treated melanocytes were easier to adhere to the dishes and move. into the filters in a dose-dependent manner, but when the dose of MSF was higher than 150 microg/ml, the adhesion and migration could not be significantly increased. And it was noticed that when the concentrations of MSF was 10microg/ml, significant statistical difference did show between the migration of the treated and untreated melanocytes (P<0.05) though the adhesion was not in-creased significantly. Conclusion: MSF had the ability to affect melanocyte adhesion and migration. This could explain, in part, the mechanism of MSF in curing vitiligo lesions. This abstract was translated into English by the publisher or author. [ABSTRACT FROM AUTHOR]

A mine-used multi-resolution display board was designed according to principle of human visual engineering and mine users' actual demands. The display board can change font resolution according to field condition so as to meet requirements of most mines.

Immunotherapy involving PDL1 degradation holds great potential in anti-tumor treatment. Optimal design of PDL1 degraders and subsequent efficient delivery into tumors are essential for expected efficacy, especially when abnormal tumor vasculature is considered. Herein, a nanodroplet-based novel drug delivery platform termed as NDs mTx (nanodroplet-based therapeutics) for ultrasound targeted delivery of PDL1 degrader is designed. Briefly, the shell of the NDs mTx is armed with RGD and mPD1 (a bioorthogonal PD1 mutant produced by genetic codon expansion technology can covalently bind PDL1), and the core is composed of perfluorohexane (PFH, C6F14). The RGD on the NDs mTx recognizes αvβ3 expressed by tumor vasculature, making NDs mTx accumulated in tumor practical and visible by low-frequency ultrasound (LFUS). In turn, inertial cavitation induced by LFUS facilitates mPD1 on the nanodroplet debris penetrating the tumor, where mPD1 covalently binds PDL1 and initiates a lysosomal degradation process. Through both in vitro and in vivo study, the superior performance of NDs mTx in degrading PDL1 and boosting anti-tumor immunity is confirmed. In conclusion, NDs mTx emerge as an alternative to existing PDL1 blockers in tumor immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Owing to its prominent π-delocalization and stability, vinylene linkage holds great merits in the construction of covalent organic frameworks (COFs) with promising semiconducting properties. However, carbon-carbon double bond formation reaction always exhibits relatively low reversibility, unfavorable for the formation of high crystalline frameworks through self-error correction and assembling processes. In this work, we report a heteroatom-tuned strategy to build up a series of two-dimensional (2D) vinylene-linked COFs by Knoevenagel condensation of an electron-deficient methylthiazolyl-based monomer with different triformyl substituted (hetero-)aromatic derivatives. The resulting COFs show high-quality periodic mesoporous structures with high surface areas. Embedding heteroatoms into the backbones enables significantly improving their crystallinity, and finely tailoring their semiconducting structures. Upon visible light stimulation, one of the as-prepared COFs with donor-π-acceptor structure could deliver a nearly seven-fold increase in the catalytic activity of hydrogen generation as compared with the other two. Meanwhile, in combination with high crystallinity and the matched conduction band energy level, such kind of COFs can be able to selectively generate singlet oxygen and superoxide radicals in a high ratio of up to 30 : 1, allowing for catalyzing aerobic thioanisole oxidation in distinctly tunable activities through the substituent electronic effect of the substrates., (© 2024 Wiley-VCH GmbH.)

Background: Wastewater is a major source of Antibiotic-Resistant Bacteria (ARB) and a hotspot for the exchange of Antibiotic-Resistant Genes (ARGs). The occurrence of Carbapenem-Resistant Bacteria (CRB) in wastewater samples is a major public health concern. Objectives: This study aimed to analyze Antibiotic resistance in bacteria from wastewater sources in Pakistan. Methods: We analyzed 32 bacterial isolates, including 18 Escherichia coli , 4 Klebsiella pneumoniae , and 10 other bacterial isolates using phenotypic antibiotic susceptibility assay and whole-genome sequencing. This study identified the ARGs, plasmid replicons, and integron genes cassettes in the sequenced isolates. One representative isolate was further sequenced using Illumina and Oxford nanopore sequencing technologies. Results: Our findings revealed high resistance to clinically important antibiotics: 91% of isolates were resistant to cefotaxime, 75% to ciprofloxacin, and 62.5% to imipenem, while 31% showed non-susceptibility to gentamicin. All E. coli isolates were resistant to cephalosporins, with 72% also resistant to carbapenems. Sequence analysis showed a diverse resistome, including carbapenamases (blaNDM-5, blaOXA-181), ESBLs (blaCTX-M-15, blaTEM), and AmpC-type β-lactamases (blaCMY). Key point mutations noticed in the isolates were pmrB&#95;Y358N (colistin) and ftsI&#95;N337NYRIN, ftsI&#95;I336IKYRI (carbapenem). The E. coli isolates had 11 different STs, with ST410 predominating (28%). Notably, the E. coli phylogroup A isolate 45EC1, (ST10886) is reported for the first time from wastewater, carrying blaNDM-5, blaCMY-16, and pmrB&#95;Y358N with class 1 integron gene cassette of dfrA 12- aadA 2- qacEΔ1 on a plasmid-borne contig. Other carbapenamase, blaNDM-1 and blaOXA-72, were detected in K. pneumoniae 22EB1 and Acinetobacter baumannii 51AC1, respectively. The integrons with the gene cassettes encoding antibiotic resistance, and the transport and bacterial mobilization protein, were identified in the sequenced isolates. Ten plasmid replicons were identified, with IncFIB prevalent in 53% of isolates. Combined Illumina and Oxford nanopore sequencing revealed blaNDM-5 on an IncFIA/IncFIC plasmid and is identical to those reported in the USA, Myanmar, and Tanzania. Conclusions: These findings highlight the environmental prevalence of high-risk and WHO-priority pathogens with clinically important ARGs, underscoring the need for a One Health approach to mitigate ARB isolates.

In the domain of control engineering, effectively tuning the parameters of proportional-integral-derivative (PID) controllers has persistently posed a challenge. This study proposes a hybrid algorithm (HGJGSO) that combines golden jackal optimization (GJO) and golden sine algorithm (Gold-SA) for tuning PID controllers. To accelerate the convergence of GJO, a nonlinear parameter adaptation strategy is incorporated. The improved GJO is combined with Gold-SA, capitalizing on the expedited convergence speed offered by the improved GJO, coupled with the global optimization and precise search capabilities of Gold-SA. HGJGSO maximizes the strengths of two algorithms, facilitating a comprehensive and balanced exploration and exploitation. The effectiveness of HGJGSO is assessed through tuning the PID controllers for three typical systems. The results indicate that HGJGSO surpasses the comparison tuning methods. To evaluate the applicability of HGJGSO, it is used to tune the cascade PID controllers for trajectory tracking in a quadrotor UAV. The results demonstrate the superiority of HGJGSO in addressing practical challenges., (© 2024. The Author(s).)

Background: Vunakizumab, a novel anti-interleukin-17A antibody, has shown promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial., Objective: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population., Methods: Six hundred ninety subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4, and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16, and every 4 weeks thereafter). The co-primary endpoints were ≥90% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12., Results: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%), and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P < .0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects., Limitations: Chinese subjects only; no active comparator., Conclusion: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis., Competing Interests: Conflicts of interest Drs Cui, Yao, Bai, and Dong were employees of Jiangsu Hengrui Pharmaceuticals at the time of study. The other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: To explore aortic stiffness measured by carotid femoral-pulse wave velocity (cf-PWV) at different stages of normal glucose, prediabetes, and diabetes mellitus (DM)., Methods: The literature comparing aortic stiffness (AS) with cf-PWV between DM and non-DM samples was systematically retrieved from Pubmed, Ovid Medline, Web of Science, Embase, Scopus, CNKI, and Wanfang databases. The Newcastle-Ottawa Scale was used to assess the quality of the literature. The primary endpoint was the mean difference (MD) of cf-PWV between the normal glucose and DM samples and normal glucose and prediabetes samples. The secondary endpoints were the MD of carotid intima-media thickness (cIMT) and carotid-radial pulse wave velocity (cr-PWV). Aggregated MD and 95% confidence intervals were calculated. When the I 2 value was >50% or p < 0.01, the heterogeneity was considered large, and the random-effect model was used; otherwise, the fixed-effect model was used. A sensitivity analysis was conducted to identify the source of heterogeneity, and a funnel plot and the regression Egger test was utilized to assess the publication bias., Results: A total of 37 studies were finally enrolled. Samples with DM had a higher cf-PWV value and cIMT value than those without DM, and the differences were statistically significant. The cr-PWV measurements tended to be higher in the DM group than in the non-DM group, but the difference was not significant. Samples with prediabetes also had a significantly higher cf-PWV value than samples with normal glucose., Conclusions: Samples with DM and prediabetes were associated with a higher cf-PWV value, indicating that DM patients had a higher central AS. Central AS progresses at the prediabetes stage. These data provide insight into understanding the mechanism of adverse effects of DM and prediabetes on artery stiffness., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Rubisco small subunit (RbcS), a core component with crucial effects on the structure and kinetic properties of the Rubisco enzyme, plays an important role in response to plant growth, development, and various stresses. Although Rbcs genes have been characterized in many plants, their muti-functions in soybeans remain elusive. In this study, a total of 11 GmRbcS genes were identified and subsequently divided into three subgroups based on a phylogenetic relationship. The evolutionary analysis revealed that whole-genome duplication has a profound effect on GmRbcSs . The cis-acting elements responsive to plant hormones, development, and stress-related were widely found in the promoter region. Expression patterns based on the RT-qPCR assay exhibited that GmRbcS genes are expressed in multiple tissues, and notably Glyma.19G046600 ( GmRbcS8 ) exhibited the highest expression level compared to other members, especially in leaves. Moreover, differential expressions of GmRbcS genes were found to be significantly regulated by exogenous plant hormones, demonstrating their potential functions in diverse biology processes. Finally, the function of GmRbcS8 in enhancing soybean resistance to soybean mosaic virus (SMV) was further determined through the virus-induced gene silencing (VIGS) assay. All these findings establish a strong basis for further elucidating the biological functions of RbcS genes in soybeans.

Background: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening., Methods: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated., Results: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI., Conclusions: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers., (© 2024. The Author(s).)

In this study, we successfully developed two novel vinylene-linked covalent organic frameworks (COFs) using 2-connected 3,6-dimethylpyridazine through Knoevenagel condensation. These COFs featured finely tailored micro-/nano-scale pore sizes, high surface areas and stable non-polar vinylene linkages. Finely resolved powder X-ray diffraction patterns demonstrated highly crystalline structures with a hexagonal lattice in the AA layer stacking. The resulting one-dimensional channels possess strong hydrogen-bond accepting sites arising from the decorated cis-azo/azine units with two pairs of fully exposed lone pair electrons, endowing the as-prepared COFs with exceptional water absorption properties. The g-DZPH-COF exhibited successive steep water uptake steps starting from low relative pressures (P/P STA =0.1), with the remarkable water uptake capacity of 0.26 g/g at P/P STA =0.2 (25 °C), which is the optimal value recorded among the reported COFs. Dynamic vapour sorption measurements revealed the fast kinetics of these COFs, even in the cluster formation process. Water uptake and release cycling tests demonstrated their outstanding hydrolytic stability, durability, and adsorption-desorption retention ability., (© 2024 Wiley-VCH GmbH.)

In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the  stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99%) and e.r. values (up to 99:1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FADox) / semiquinone state (FADsq) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of CvFAP promiscuity, and thus expands the reactivity repertoire of CvFAP and highlights the versatility of CvFAP in asymmetric synthesis., (© 2024 Wiley‐VCH GmbH.)

Introduction: The enteric microbiome and its possible modulation to improve feed conversion or vaccine efficacy is gaining more attention in pigs. Weaning pigs from their dam, along with many routine procedures, is stressful. A better understanding of the impact of this process on the microbiome may be important for improving pig production. The objective of this study was to develop a weaner pig cannulation model, thus allowing ileum content collection from the same pig over time for 16S rRNA sequencing under different porcine reproductive and respiratory syndrome virus (PRRSV) infection statuses., Methods: A total of 15 3-week-old pigs underwent abdominal surgery and were fitted with an ileum cannula, with ileum contents collected over time. In this pilot study, treatment groups included a NEG-CONTROL group (no vaccination, no PRRSV challenge), a POS-CONTROL group (no vaccination, challenged with PRRSV), a VAC-PRRSV group (vaccinated, challenged with PRRSV), a VAC-PRO-PRRSV group (vaccinated, supplemented with a probiotic, challenged with PRRSV), and a VAC-ANTI-PRRSV group (vaccinated, administered an antibiotic, challenged with PRRSV). We assessed the microbiome over time and measured anti-PRRSV serum antibodies, PRRSV load in serum and nasal samples, and the severity of lung lesions., Results: Vaccination was protective against PRRSV challenge, irrespective of other treatments. All vaccinated pigs mounted an immune response to PRRSV within 1 week after vaccination. A discernible impact of treatment on the diversity, structure, and taxonomic abundance of the enteric microbiome among the groups was not observed. Instead, significant influences on the ileum microbiome were observed in relation to time and treatment., Discussion: The cannulation model described in this pilot study has the potential to be useful in studying the impact of weaning, vaccination, disease challenge, and antimicrobial administration on the enteric microbiome and its impact on pig health and production. Remarkably, despite the cannulation procedures, all vaccinated pigs exhibited robust immune responses and remained protected against PRRSV challenge, as evidenced by the development of anti-PRRSV serum antibodies and viral shedding data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Opriessnig, Halbur, Bayne, Rawal, Tong, Mou, Li, Zhang, Zhang and Muwonge.)

Background: For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON)., Methods: Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups., Results: A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study., Conclusions: Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Ophthalmology Society.)

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes., (© 2024. The Author(s).)

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China., Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date., Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full., Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health. These manifestations are influenced by systemic inflammation, oxidative stress, and hormonal imbalances, all hallmarks of COPD. Recent research has uncovered an intricate interplay between COPD and musculoskeletal comorbidities, suggesting that muscle and bone tissues may cross-communicate through the release of signalling molecules, known as "myokines" and "osteokines". We explored this dynamic relationship, with a particular focus on the role of the immune system in mediating the cross-communication between muscle and bone in COPD. Moreover, we delved into existing and emerging therapeutic strategies for managing musculoskeletal disorders in COPD. It underscores the development of personalized treatment approaches that target both the respiratory and musculoskeletal aspects of COPD, offering the promise of improved well-being and quality of life for individuals grappling with this complex condition. This comprehensive review underscores the significance of recognizing the profound impact of COPD on the musculoskeletal system and its comorbidities. By unravelling the intricate connections between these systems and exploring innovative treatment avenues, we can aspire to enhance the overall care and outcomes for COPD patients, ultimately offering hope for improved health and well-being., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Idiopathic pulmonary fibrosis (IPF) causes progressive lung scarring and high mortality. Reliable and accurate prognostic biomarkers are urgently needed. Objectives: To identify and validate circulating protein biomarkers of IPF survival. Methods: High-throughput proteomic data were generated using prospectively collected plasma samples from patients with IPF from the Pulmonary Fibrosis Foundation Patient Registry (discovery cohort) and the Universities of California, Davis; Chicago; and Virginia (validation cohort). Proteins associated with three-year transplant-free survival (TFS) were identified using multivariable Cox proportional hazards regression. Those associated with TFS after adjustment for false discovery in the discovery cohort were advanced for testing in the validation cohort, with proteins maintaining TFS association with consistent effect direction considered validated. After combining cohorts, functional analyses were performed, and machine learning was used to derive a proteomic signature of TFS. Measurements and Main Results: Of 2,921 proteins tested in the discovery cohort ( n  = 871), 231 were associated with differential TFS. Of these, 140 maintained TFS association with consistent effect direction in the validation cohort ( n  = 355). After cohorts were combined, the validated proteins with the strongest TFS association were latent-transforming growth factor β-binding protein 2 (hazard ratio [HR], 2.43; 95% confidence interval [CI] = 2.09-2.82), collagen α-1(XXIV) chain (HR, 2.21; 95% CI = 1.86-2.39), and keratin 19 (HR, 1.60; 95% CI = 1.47-1.74). In decision curve analysis, a proteomic signature of TFS outperformed a similarly derived clinical prediction model. Conclusions: In the largest proteomic investigation of IPF outcomes performed to date, we identified and validated 140 protein biomarkers of TFS. These results shed important light on potential drivers of IPF progression.

Stereodivergent engineering of one enzyme to create stereocomplementary variants for synthesizing optically pure molecules with tailor-made (R) or (S) configurations on an optional basis is highly desirable and challenging. This study aimed to engineer fatty acid photodecarboxylase from Chlorella variabilis (CvFAP) using the focused rational iterative site-specific mutagenesis (FRISM) strategy to obtain two highly stereocomplementary variants with excellent selectivity (both giving products with up to 99 % e.e.). These variants were used for the CvFAP-catalyzed light-driven kinetic resolution of oxalates or oxamic acids prepared from the corresponding sec-alcohols or amines, providing a new biotransformation process for preparing chiral sec-alcohols and amines. Molecular dynamics simulation, kinetic data and transient spectra revealed the source of selectivity. This study represents the first example of the kinetic resolution of sec-alcohols or amines catalyzed by a pair of stereocomplementary CvFAPs., (© 2024 Wiley-VCH GmbH.)

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation ( Nlgn3 R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3 R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3 R451C mice show a 30.9% faster gastrointestinal transit ( p = 0.0004) in vivo and have 6% longer small intestines ( p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3 R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3 R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABA A antagonist, gabazine, compared to 40.6% in wild-type mice ( p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3 R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3 R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

In clinical trials, unilateral or bilateral data can usually be encountered if a subject contributes one or both of paired organs. For the bilateral data, responses from two paired body parts are correlated. In this paper, we study various confidence intervals of common risk difference in stratified unilateral and bilateral data based on the Dallal's model. Simulation results show that the score method outperforms other methods and provides coverage probability close to the nominal level and satisfactory coverage width. Hence, the method is recommended. In addition, the inverse hyperbolic tangent Wald-type become as optimal as the score method with the increase of sample sizes. An otolaryngology example is used to demonstrate the proposed methods.

Background: Elevated IL-21 expression which can effectively induce Th17 cell differentiation has been implicated in the pathogenesis of psoriasis, but its role in angiogenesis remains poorly understood., Methods: PASI and PSI score assessment was applied to evaluate the severity of psoriatic lesions. The expression of IL-21, IL-21 receptor (IL-21R), CD31, VEGFA, MMP-9, and ICAM-1 in skin was determined by immunohistochemistry or quantitative real-time polymerase chain reaction. The serum level of IL-21 was measured by enzyme-linked immunosorbent assay (ELISA). Then, their correlation was analyzed statistically. Human umbilical vein endothelial cells (HUVECs) cocultured with conditional medium from normal human epidermal keratinocytes (NHEKs) were treated with IL-21 and/or M5 cocktail (mixture of IL-1α, IL-17A, IL-22, TNF-α, and oncostatin M). The migration and tube formation of HUVECs were detected, and the levels of VEGFA, MMP-9, and ICAM-1 in NHEKs were measured by Western blotting or ELISA., Results: Increased IL-21 and IL-21R expression was observed in psoriatic sera or skin specimens, with IL-21R mainly locating in keratinocytes and IL-21 in immune cells. Pearson analysis showed significantly positive correlation between IL-21/IL-21R and erythema scores/microvessel density in psoriatic lesions. Moreover, the expression of proangiogenic genes, VEGFA, ICAM-1, and MMP-9 was upregulated in skins of psoriasis. Additionally, in M5 microenvironment, migration and tube formation could be magnified in HUVECs using IL-21 pre-treated NHEK medium. Mechanically, the co-stimulation of IL-21 and M5 to NEHKs increased the expression of ICAM-1., Conclusion: IL-21 could regulate keratinocytes to secrete ICAM-1, thereby promoting angiogenesis in psoriasis., (© 2023 Federation of American Societies for Experimental Biology.)

Importance: This study highlights a Streptococcus equi subspecies zooepidemicus ( S. zooepidemicus ) strain isolated from an outbreak in Indiana, which resulted in mortality events among a swine herd in 2021. The Indiana outbreak strain was found to be genetically and phylogenetically distant to a strain isolated from the 2019 outbreaks in Ohio and Tennessee, which caused high swine mortality. We also discovered multiple unique genetic features in the Indiana outbreak strain, including distinct S. zooepidemicus genomic islands, and notable S. zooepidemicus virulence genes-many of which could serve as biomarkers for the diagnosis of this strain. These findings provide significant insights into monitoring and potentially preventing severe outbreaks caused by the Indiana outbreak strain in the future., Competing Interests: The authors declare no conflict of interest.

Background: Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients., Methods: Peripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays., Results: We identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway., Conclusion: This study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Luan, Li, Niu, He, Zhao, Chen, Mao, Mou and Li.)

Background: The medial patellofemoral ligament (MPFL) is the most important stabilizer of lateral dislocation of the patella. Single-limb (SL) and double-limb (DL) graft MPFL reconstructions have been increasingly used to treat recurrent patellar dislocations, but the clinical efficacy of SL versus DL graft MPFL reconstructions remains controversial owing to the inconsistent conclusions of previous studies., Purpose: This study aimed to compare the clinical outcomes of SL and DL graft MPFL reconstructions for patients with recurrent patellar dislocation by conducting a meta-analysis of randomized controlled trials and cohort studies., Study Design: Meta-analysis; Level of evidence, 3., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for relevant studies. The retrieval time was up to July 25, 2022. Two evaluators independently screened the literature, extracted data, and assessed the methodological quality of the enrolled studies. Meta-analysis was conducted using RevMan 5.4 software., Results: A total of 4 randomized controlled trials and 3 cohort studies with 451 patients were included. The joint stability and functional scores in both groups improved significantly from baseline. When compared with SL graft reconstruction, DL graft reconstruction provided reduced recurrent instability ( P = .01), anterior patella-related pain ( P = .02), and patellar lateral shift rate ( P = .02). Regarding functional recovery, patients undergoing DL graft reconstruction presented better scores on the Kujala ( P < .001), Tegner ( P = .009), and International Knee Documentation Committee (IKDC) ( P < .001) but similar Lysholm scores as compared with SL graft reconstruction. No statistically significant difference was found between the techniques in the reduction of the patellar tilt angle, complications other than anterior patella-related pain, or postoperative pain., Conclusion: When compared with SL graft MPFL reconstruction, DL graft MPFL reconstruction yielded better outcomes in terms of postoperative recurrent instability, anterior patella-related pain, patellar lateral shift rate, Kujala score, Tegner score, and IKDC score. The amount of high-quality evidence is insufficient, so this conclusion should be interpreted with caution., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Ocular manifestations have been well recognized in coronavirus disease 2019 (COVID-19) outbreak. Several studies have detected ocular manifestations in patients after COVID-19. However, little is known about the retinal and vitreal alterations in patients before and after COVID-19 infection. This study aimed to investigate the retinal and vitreal alterations in patients before and after contracting COVID-19 infection using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). A total of 38 participants (76 eyes) were enrolled and followed-up 1 month after COVID-19 infection. Then, 26 patients (52 eyes) were evaluated 3 months after COVID-19 infection. Compared with the pre-COVID-19 status, patients with 1- and 3-month post-COVID-19 statuses had significant thinning of ganglion cell and inner plexiform layer, thickening of inner nuclear layer, a decrease in the vessel density (VD) of superficial vascular complex, and an increase in the VD of deep vascular complex. Meanwhile, alteration in parameters of foveal avascular zone (all p < 0.05) and hyper-reflective dots in the vitreous of 27 patients (54 eyes) (71.1% vs. pre-COVID-19, 34.2%, p = 0.006) were observed. These findings suggest significantly retinal and vitreal alterations occurred in patients after COVID-19 infection, possibly due to direct or indirect virus-induced injuries. Further longitudinal studies are required to investigate the long-term effects of COVID-19 infection on the human eyes., (© 2023 Wiley Periodicals LLC.)

Background: Vitiligo has been correlated with an abnormal gut microbiota. We aimed to systematically identify characteristics of the gut microbial compositions, genetic functions, and potential metabolic features in patients with non-segmental vitiligo., Methods: Twenty-five patients with non-segmental vitiligo and 25 matched healthy controls (HCs) were enrolled. Metagenomic sequencing and bioinformatic analysis were performed to determine the gut microbiota profiles. Differences in gut microbiota diversity and composition between patients with vitiligo and HCs were analyzed. Gene functions and gut metabolic modules were predicted with the Kyoto Encyclopedia of Gene and Genomes (KEGG) and MetaCyc databases., Results: Compared with HCs, alpha diversity of intestinal microbiome in vitiligo patients was significantly reduced. At the species level, the relative abundance of Staphylococcus thermophiles was decreased, and that of Bacteroides fragilis was increased in patients with vitiligo compared with those of the HCs. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed representative microbial markers of Lachnospiraceae&#95;bacterium&#95;BX3, Massilioclostridium&#95;coli, TM7&#95;phylum&#95;sp&#95;oral&#95;taxon&#95;348 and Bacteroides&#95;fragilis for patients with vitiligo. KEGG gene function analysis showed that the NOD-like receptor signaling pathway was significantly enriched in patients with vitiligo. Gut metabolic modules (GMMs) analysis showed that cysteine degradation was significantly down-regulated, and galactose degradation was up-regulated in patients with vitiligo. A panel of 28 microbial features was constructed to distinguish patients with vitiligo from HCs., Conclusions: The gut microbial profiles and genetic functions of patients with vitiligo were distinct from those of the HCs. The identified gut microbial markers may potentially be used for earlier diagnosis and treatment targets., (© 2023. BioMed Central Ltd., part of Springer Nature.)