Functional Characterization of the MeSSIII-1 Gene and Its Promoter from Cassava.

Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the MeSSIII-1 gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the MeSSIII-1 gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots. MeSSIII-1 expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava. MeSSIII-1 expression patterns were further confirmed in proMeSSIII-1 transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp MeSSIII-1 promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the MeSSIII-1 gene and for further in-depth exploration of the regulatory network of its internal functional elements.

Phycocyanin from microalgae: A comprehensive review covering microalgal culture, phycocyanin sources and stability.

As food safety continues to gain prominence, phycocyanin (PC) is increasingly favored by consumers as a natural blue pigment, which is extracted from microalgae and serves the dual function of promoting health and providing coloration. Spirulina-derived PC demonstrates exceptional stability within temperature ranges below 45 °C and under pH conditions between 5.5 and 6.0. However, its application is limited in scenarios involving high-temperature processing due to its sensitivity to heat and light. This comprehensive review provides insights into the efficient production of PC from microalgae, covers the metabolic engineering of microalgae to increase PC yields and discusses various strategies for enhancing its stability in food applications. In addition to the most widely used Spirulina, some red algae and Thermosynechococcus can serve as good source of PC. The genetic and metabolic manipulation of microalgae strains has shown promise in increasing PC yield and improving its quality. Delivery systems including nanoparticles, hydrogels, emulsions, and microcapsules offer a promising solution to protect and extend the shelf life of PC in food products, ensuring its vibrant color and health-promoting properties are preserved. This review highlights the importance of metabolic engineering, multi-omics applications, and innovative delivery systems in unlocking the full potential of this natural blue pigment in the realm of food applications, provides a complete overview of the entire process from production to commercialization of PC, including the extraction and purification.

Revealing nitrogenous VX metabolites and the whole-molecule VX metabolism in the urine of guinea pigs.

VX, a well-known organophosphorus nerve agent (OPNA), poses a significant threat to public safety if employed by terrorists. Obtaining complete metabolites is critical to unequivocally confirm its alleged use/exposure and elucidate its whole-molecular metabolism. However, the nitrogenous VX metabolites containing 2-diisopropylaminoethyl moiety from urinary excretion remain unknown. Therefore, this study applied a newly developed untargeted workflow platform to discover and identify them using VX-exposed guinea pigs as animal models. 2-(N,N-diisopropylamino)ethanesulfonic acid (DiPSA) was revealed as a novel nitrogenous VX metabolite in urine, and 2-(Diisopropylaminoethyl) methyl sulfide (DAEMS) was confirmed as another in plasma, indicating that VX metabolism differed between urine and plasma. It is the first report of a nitrogenous VX metabolite in urine and a complete elucidation of the VX metabolic pathway. DiPSA was evaluated as an excellent VX exposure biomarker. The whole-molecule VX metabolism in urine was characterized entirely for the first time via the simultaneous quantification of DiPSA and two known P-based biomarkers. About 52.1% and 32.4% of VX were excreted in urine as P-based and nitrogenous biomarkers within 24 h. These findings provide valuable insights into the unambiguous detection of OPNA exposure/intoxication and human and environmental exposure risk assessment.

Public Restroom Access and Mental Health Among Gender-Minoritized Individuals in China.

This cross-sectional study assesses the adequacy of gender-neutral public restrooms and examines the association of public restroom­related stress with mental health among gender-diverse individuals in China.

Superhydrophobic, Highly Conductive, and Trilayered Fabric with Connected Carbon Nanotubes for Energy-Efficient Electrical Heating.

Current electrically heated fabrics provide heat in cold climates, suffer from abundant wasted radiant heat energy to the external environment, and are prone to damage by water. Thus, constructing energy-efficient and superhydrophobic conductive fabrics is in high demand. Therefore, we propose an effective and facile methodology to prepare a superhydrophobic, highly conductive, and trilayered fabric with a connected carbon nanotube (CNT) layer and a titanium dioxide (TiO2) nanoparticle heat-reflecting layer. We construct polyamide/fluorinated polyurethane (PA/FPU) nanofibrous membranes via first electrospinning, then performing blade-coating with the polyurethane (PU) solution with CNTs, and finally fabricating FPU/TiO2 nanoparticles via electrospraying. This strategy causes CNTs to be connected to form a conductive layer and enables TiO2 nanoparticles to be bound together to form a porous, heat-reflecting layer. As a consequence, the as-prepared membranes demonstrate high conductivity with an electrical conductivity of 63 S/m, exhibit rapid electric-heating capacity, and exhibit energy-efficient asymmetrical heating behavior, i.e., the heating temperature of the PA/FPU nanofibrous layer reaches more than 83 °C within 90 s at 24 V, while the heating temperature of the FPU/TiO2 layer only reaches 53 °C, as well as prominent superhydrophobicity with a water contact angle of 156°, indicating promising utility for the next generation of electrical heating textiles.

Establishment and Verification of an Artificial Intelligence Prediction Model for Children With Sepsis.

BACKGROUND: Early identification of high-risk groups of children with sepsis is beneficial to reduce sepsis mortality. This article used artificial intelligence (AI) technology to predict the risk of death effectively and quickly in children with sepsis in the pediatric intensive care unit (PICU). STUDY DESIGN: This retrospective observational study was conducted in the PICUs of the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2019 and Shenzhen Children's Hospital from January 2019 to July 2020. The children were divided into a death group and a survival group. Different machine language (ML) models were used to predict the risk of death in children with sepsis. RESULTS: A total of 671 children with sepsis were enrolled. The accuracy (ACC) of the artificial neural network model was better than that of support vector machine, logical regression analysis, Bayesian, K nearest neighbor method and decision tree models, with a training set ACC of 0.99 and a test set ACC of 0.96. CONCLUSIONS: The AI model can be used to predict the risk of death due to sepsis in children in the PICU, and the artificial neural network model is better than other AI models in predicting mortality risk.

Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury.

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.

Reliability and validity tests of the Chinese version of the Geriatric Locomotive Function Scale (GLFS-25) in tumor survivors.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.

Synthesis of Flavonols and Assessment of Their Biological Activity as Anticancer Agents.

A series of flavanols were synthesized to assess their biological activity against human non-small cell lung cancer cells (A549). Among the sixteen synthesized compounds, it was observed that compounds 6k (3.14 ± 0.29 µM) and 6l (0.46 ± 0.02 µM) exhibited higher potency compared to 5-fluorouracil (5-Fu, 4.98 ± 0.41 µM), a clinical anticancer drug which was used as a positive control. Moreover, compound 6l (4'-bromoflavonol) markedly induced apoptosis of A549 cells through the mitochondrial- and caspase-3-dependent pathways. Consequently, compound 6l might be developed as a candidate for treating or preventing lung cancer.

MELK aggravates lung adenocarcinoma by regulating EZH2 ubiquitination and H3K27me3 histone methylation of LATS2.

We tried to elucidate the possible roles of maternal embryonic leucine pull chain kinase (MELK) in lung adenocarcinoma (LUAD) growth and metastasis. Differentially expressed genes in LUAD samples were analysed by the GEPIA database. Clinical tissue samples and cells were collected for MELK, EZH2 and LATS2 expression determination. Co-IP assay was used to verify the interaction between EZH2 and MELK; CHX tracking assay and ubiquitination assay detected the degradation of MELK on EZH2 ubiquitination. ChIP assay detected the enrichment of EZH2 and H3K27me3 on the LATS2 promoter region. LUAD cells were selected for in vitro validation, and the tumorigenic ability of LUAD cells was also observed in a transplantation tumour model of LUAD nude mice. MELK and EZH2 were highly expressed in LUAD samples, while LATS2 was lowly expressed. MELK interacted with EZH2 to inhibit its ubiquitination degradation; EZH2 elevated H3K27me3 modification in the LATS2 promoter to lower LATS2 expression. Silencing MELK or EZH2 or overexpressing LATS2 restrained LUAD cell proliferation and invasion, and facilitated their apoptosis. Silencing MELK or EZH2 or overexpressing LATS2 suppressed tumour formation in nude mice. This study demonstrated that MELK aggravated LUAD by upregulating EZH2 and downregulating LATS2.

Exploration of agr types, virulence-associated genes, and biofilm formation ability in Staphylococcus aureus isolates from hemodialysis patients with vascular access infections.

Introduction: Staphylococcus aureus, is a pathogen commonly encountered in both community and hospital settings. Patients receiving hemodialysis treatment face an elevated risk of vascular access infections (VAIs) particularly Staphylococcus aureus, infection. This heightened risk is attributed to the characteristics of Staphylococcus aureus, , enabling it to adhere to suitable surfaces and form biofilms, thereby rendering it resistant to external interventions and complicating treatment efforts. Methods: Therefore this study utilized PCR and microtiter dish biofilm formation assay to determine the difference in the virulence genes and biofilm formation among in our study collected of 103 Staphylococcus aureus, isolates from hemodialysis patients utilizing arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs) during November 2013 to December 2021. Results: Our findings revealed that both MRSA and MSSA isolates exhibited strong biofilm production capabilities. Additionally, we confirmed the presence of agr types and virulence genes through PCR analysis. The majority of the collected isolates were identified as agr type I. However, agr type II isolates displayed a higher average number of virulence genes, with MRSA isolates exhibiting a variety of virulence genes. Notably, combinations of biofilm-associated genes, such as eno-clfA-clfB-fib-icaA-icaD and eno-clfA-clfB-fib-fnbB-icaA-icaD, were prevalent among Staphylococcus aureus, isolates obtained from vascular access infections. Discussion: These insights contribute to a better understanding of the molecular characteristics associated with Staphylococcus aureus, infections in hemodialysis patients and provided more targeted and effective treatment approaches.

Lesion attention guided neural network for contrast-enhanced mammography-based biomarker status prediction in breast cancer.

BACKGROUND AND OBJECTIVE: Accurate identification of molecular biomarker statuses is crucial in cancer diagnosis, treatment, and prognosis. Studies have demonstrated that medical images could be utilized for non-invasive prediction of biomarker statues. The biomarker status-associated features extracted from medical images are essential in developing medical image-based non-invasive prediction models. Contrast-enhanced mammography (CEM) is a promising imaging technique for breast cancer diagnosis. This study aims to develop a neural network-based method to extract biomarker-related image features from CEM images and evaluate the potential of CEM in non-invasive biomarker status prediction. METHODS: An end-to-end learning convolutional neural network with the whole breast images as inputs was proposed to extract CEM features for biomarker status prediction in breast cancer. The network focused on lesion regions and flexibly extracted image features from lesion and peri­tumor regions by employing supervised learning with a smooth L1-based consistency constraint. An image-level weakly supervised segmentation network based on Vision Transformer with cross attention to contrast images of breasts with lesions against the contralateral breast images was developed for automatic lesion segmentation. Finally, prediction models were developed following further selection of significant features and the implementation of random forest-based classification. Results were reported using the area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A dataset from 1203 breast cancer patients was utilized to develop and evaluate the proposed method. Compared to the method without lesion attention and with only lesion regions as inputs, the proposed method performed better at biomarker status prediction. Specifically, it achieved an AUC of 0.71 (95 % confidence interval [CI]: 0.65, 0.77) for Ki-67 and 0.73 (95 % CI: 0.65, 0.80) for human epidermal growth factor receptor 2 (HER2). CONCLUSIONS: A lesion attention-guided neural network was proposed in this work to extract CEM image features for biomarker status prediction in breast cancer. The promising results demonstrated the potential of CEM in non-invasively predicting the biomarker statuses in breast cancer.

Advancing musculoskeletal tumor diagnosis: Automated segmentation and predictive classification using deep learning and radiomics.

OBJECTIVES: Musculoskeletal (MSK) tumors, given their high mortality rate and heterogeneity, necessitate precise examination and diagnosis to guide clinical treatment effectively. Magnetic resonance imaging (MRI) is pivotal in detecting MSK tumors, as it offers exceptional image contrast between bone and soft tissue. This study aims to enhance the speed of detection and the diagnostic accuracy of MSK tumors through automated segmentation and grading utilizing MRI. MATERIALS AND METHODS: The research included 170 patients (mean age, 58 years ±12 (standard deviation), 84 men) with MSK lesions, who underwent MRI scans from April 2021 to May 2023. We proposed a deep learning (DL) segmentation model MSAPN based on multi-scale attention and pixel-level reconstruction, and compared it with existing algorithms. Using MSAPN-segmented lesions to extract their radiomic features for the benign and malignant classification of tumors. RESULTS: Compared to the most advanced segmentation algorithms, MSAPN demonstrates better performance. The Dice similarity coefficients (DSC) are 0.871 and 0.815 in the testing set and independent validation set, respectively. The radiomics model for classifying benign and malignant lesions achieves an accuracy of 0.890. Moreover, there is no statistically significant difference between the radiomics model based on manual segmentation and MSAPN segmentation. CONCLUSION: This research contributes to the advancement of MSK tumor diagnosis through automated segmentation and predictive classification. The integration of DL algorithms and radiomics shows promising results, and the visualization analysis of feature maps enhances clinical interpretability.

Adjuvant Chemotherapy in Patients with Locally Advanced Upper Tract Urothelial Carcinoma with or without Kidney Transplantation.

Background: The incidence of upper tract urothelial carcinoma (UTUC) is uniquely high in kidney transplant (KT) recipients in Taiwan. The evidence of adjuvant chemotherapy (AC) in UTUC is contradictory. We have sought to determine whether AC is associated with potential benefits related to locally advanced UTUC after KT. Methods: We retrospectively analyzed 134 patients with locally advanced UTUC (at least stage T2) and patients who were administrated AC after unilateral or bilateral nephroureterectomy with bladder cuff excision. Of these 134 patients, 57 patients fulfilled our inclusion criteria. We used 23 KT and 34 non-KT locally advanced UTUC patients for comparison. Results: The mean follow-up time was 52.35 ± 34.56 and 64.71 ± 42.29 months for the KT and non-KT groups, respectively. The five-year disease-free survival (DFS) and overall survival (OS) rates were 45.7% vs. 70.2% and 62.8% vs. 77.6%, for the KT and non-KT groups. The Kaplan-Meier curve and the log rank test revealed significant differences in the DFS and OS rates between the two groups, p = 0.015 and 0.036. The influence of chemotherapy on graft kidney function was mild. Only three in the KT group and two in the non-KT group developed > grade 2 nephrotoxicity. Conclusions: Our study suggested that KT patients with locally advanced UTUC who had been administered AC after surgery presented worse OS and DFS than non-KT patients. KT patients tolerated the AC course well, and their nephrotoxicity levels were mild and acceptable.

Evaluation of Peregrinus maidis transformer-2 as a target for CRISPR-based control.

The corn planthopper, Peregrinus maidis, is an economically important pest of corn and sorghum. Here we report the initial steps towards developing a CRISPR-based control method, precision guided sterile insect technique (pgSIT), for this hemipteran pest. Specifically, we evaluated the potential of transformer-2 (tra-2) as a target for sterilizing insects. First, we identified tra-2 transcripts within our P. maidis transcriptome database and performed RNA interference (RNAi) to confirm functional conservation. RNAi-mediated knockdown of Pmtra-2 in nymphs transformed females into pseudomales with deformed ovipositors resembling male claspers. While males showed no overt difference in appearance, they were indeed sterile. Importantly, the results were similar to those observed in another planthopper, Nilaparvata lugens. We also used CRISPR/Cas9 genome editing to assess the impact of tra-2 knockout in injectees. CRISPR-mediated knockout of Pmtra-2 had lethal effects on embryos, and hence not many injectees reached adulthood. However, mosaic knockout of Pmtra-2 did impact female and male fertility, which supports the use of tra-2 as a target for pgSIT in this hemipteran species.

Analysis on status quo and related factors of delays in diagnosis and treatment of breast cancer in Ningxia Hui Autonomous Region.

This study aimed to explore factors contributing to the delays in the diagnosis and treatment of breast cancer (BC) in Ningxia Hui Autonomous Region. We conducted a cohort analysis of 1012 patients with BC diagnosed at the General Hospital of Ningxia Medical University between January 2018 and December 2019. Sociodemographic data were collected through questionnaires, and clinical data were gathered and analyzed from relevant databases. Furthermore, observations were made regarding delays in the diagnosis and treatment of BC, followed by an analysis of the correlations between patient delay and both sociological factors within the population and clinical factors specific to patients with BC. Subsequently, the factors associated with patient delay and system delay were examined using Cox regression analysis, along with the inclusion of neoadjuvant therapy. In the prevention and treatment of BC in Ningxia, the patient delay rate was 33.20%, the diagnosis delay rate was 17.89%, the treatment delay rate was 0.0099% and the system delay rate was 41.60%. There was a higher proportion of patient delay and system delay in aged patients (age ≥ 61 years) with rural registered permanent residence (RPR), multiple clinical symptoms (such as nipple spillage, axillary abnormalities, etc), a T4 tumor size classification, and the initial use of neoadjuvant therapy. Besides, significant positive correlations were observed between patient delay and system delay time with BC stage. Patients aged 51 to 60 and those with molecular types (Limanal1B: ki-67 > 14%, Limanal1B: HER-2 positive) were prone to patient delay, whereas molecular characteristics influenced system delay, unrelated to sociodemographic factors. The study identifies significant age, residency, and tumor molecular subtype correlations with diagnostic and treatment delays in Ningxia's patients with BC, predominantly affecting women aged 41 to 60, especially urban dwellers. These findings underscore the need for targeted interventions to reduce delays and improve BC care in this region.

Circulating cytokines levels and osteoarthritis: A Mendelian randomization study.

BACKGROUND: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. METHODS: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. RESULTS: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. CONCLUSIONS: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.

Triple-layered core-shell fiber dressings with enduring platelet conservation and sustained growth factor release abilities for chronic wound healing.

Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.

Discrepant soil microbial community and C cycling function responses to conventional and biodegradable microplastics.

Biodegradable microplastics (MPs) are promising alternatives to conventional MPs and are of high global concern. However, their discrepant effects on soil microorganisms and functions are poorly understood. In this study, polyethylene (PE) and polylactic acid (PLA) MPs were selected to investigate the different effects on soil microbiome and C-cycling genes using high-throughput sequencing and real-time quantitative PCR, as well as the morphology and functional group changes of MPs, using scanning electron microscopy and Fourier transform infrared spectroscopy, and the driving factors were identified. The results showed that distinct taxa with potential for MP degradation and nitrogen cycling were enriched in soils with PLA and PE, respectively. PLA, smaller size (150-180 µm), and 5% (w/w) of MPs enhanced the network complexity compared with PE, larger size (250-300 µm), and 1% (w/w) of MPs, respectively. PLA increased ß-glucosidase by up to 2.53 times, while PE (150-180 µm) reduced by 38.26-44.01% and PE (250-300 µm) increased by 19.00-22.51% at 30 days. Amylase was increased by up to 5.83 times by PLA (150-180 µm) but reduced by 40.26-62.96% by PLA (250-300 µm) and 16.11-43.92% by PE. The genes cbbL, cbhI, abfA, and Lac were enhanced by 37.16%- 1.99 times, 46.35%- 26.46 times, 8.41%- 69.04%, and 90.81%- 5.85 times by PLA except for PLA1B/5B at 30 days. These effects were associated with soil pH, NO3--N, and MP biodegradability. These findings systematically provide an understanding of the impact of biodegradable MPs on the potential for global climate change.