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Abstract Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.

Abstract Background Bioactive peptides are important bioactive molecules composed of short-chain amino acids that play various crucial roles in the body, such as regulating physiological processes and promoting immune responses and antibacterial effects. Due to their significance, bioactive peptides have broad application potential in drug development, food science, and biotechnology. Among them, understanding their biological mechanisms will contribute to new ideas for drug discovery and disease treatment. Results This study employs generative adversarial capsule networks (CapsuleGAN), gated recurrent units (GRU), and convolutional neural networks (CNN) as base classifiers to achieve ensemble learning through voting methods, which not only obtains high-precision prediction results on the angiotensin-converting enzyme (ACE) inhibitory peptides dataset and the anticancer peptides (ACP) dataset but also demonstrates effective model performance. For this method, we first utilized the protein language model—evolutionary scale modeling (ESM-2)—to extract relevant features for the ACE inhibitory peptides and ACP datasets. Following feature extraction, we trained three deep learning models—CapsuleGAN, GRU, and CNN—while continuously adjusting the model parameters throughout the training process. Finally, during the voting stage, different weights were assigned to the models based on their prediction accuracy, allowing full utilization of the model's performance. Experimental results show that on the ACE inhibitory peptide dataset, the balanced accuracy is 0.926, the Matthews correlation coefficient (MCC) is 0.831, and the area under the curve is 0.966; on the ACP dataset, the accuracy (ACC) is 0.779, and the MCC is 0.558. The experimental results on both datasets are superior to existing methods, demonstrating the effectiveness of the experimental approach. Conclusion In this study, CapsuleGAN, GRU, and CNN were successfully employed as base classifiers to implement ensemble learning, which not only achieved good results in the prediction of two datasets but also surpassed existing methods. The ability to predict peptides with strong ACE inhibitory activity and ACPs more accurately and quickly is significant, and this work provides valuable insights for predicting other functional peptides. The source code and dataset for this experiment are publicly available at https://github.com/Zhou-Jianren/bioactive-peptides .

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. N6-methyladenosine (m6A) is the most common mRNA modification and participates in various immune processes such as interferon production and immune cell regulation. However, the role of m6A in dysregulated immune response of SLE remains unknown. Methods PBMCs from SLE patients were collected to compare the m6A modification profile by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Interferon regulatory factor 4 (IRF4) was identified by combination with MeRIP-seq and RNA-Seq. IRF4 and methyltransferase 3 (METTL3) were detected using qRT-PCR and WB. Clinical significance of IRF4 in SLE patients was explored subsequently. IRF4 expression in B cell subsets of female MRL/lpr mice was detected by flow cytometry. Adeno-associated viruses (AAV) including AAV9-METTL3-OE and/or AAV9-IRF4-sh were treated with female MRL/lpr mice. Autoantibody levels and kidney injury were tested by ELISA, pathological staining, and immunofluorescence. m6A level of IRF4 was detected by MeRIP-qPCR. The downstream effectors of IRF4 contributing to renal pathology were explored by RNA-seq and verified by qRT-PCR. Results m6A methylation features were obviously aberrant in SLE patients, and IRF4 was the upregulated gene modified by m6A. METTL3 and IRF4 expressions were elevated in SLE patients and kidney of MRL/lpr mice. Clinical analysis indicated that SLE patients with high IRF4 level were more prone to kidney damage. IRF4 expression was especially increased in plasma cells of MRL/lpr mice. METTL3 induced renal IRF4 expression, plasma creatinine, ANA and urine ALB levels, IgG and C3 deposition, and renal damage and plasma cell infiltration were aggravated in MRL/lpr mice. However, IRF4 depletion could partially reduce METTL3-induced kidney damage. Meanwhile, m6A level of IRF4 elevated with METTL3 overexpression. Also, the expression of Cxcl1, Bcl3, and Fos mRNA were significantly reduced after knockdown of IRF4, which were mainly involved in TNF signaling pathway. Conclusions Our study confirmed that upregulated METTL3 promoting IRF4 expression in an m6A-dependent manner, thus causing plasma cell infiltration-mediated kidney damage of SLE. This provides new evidence for the role of m6A in SLE kidney injury.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by xanthomatous infiltration of affected organs. We present a case of a 62-year-old man with ECD initially presenting with constrictive pericarditis. Comprehensive imaging revealed systemic involvement, including the skeleton, orbit, pituitary, lung, kidney, and retroperitoneum, despite the absence of related symptoms. The diagnosis of ECD was eventually confirmed through histopathological evidence from a CT-guided biopsy. The patient responded well to interferon-α2b treatment, with gradual symptom amelioration and improvement in imaging and laboratory findings over a 5-month follow-up period. This case highlights the importance of considering ECD in the differential diagnosis of constrictive pericarditis and the utility of multimodal imaging for accurate diagnosis and management of this rare disease. The patient's positive response to treatment also highlights the potential for effective management of ECD, particularly with early diagnosis and intervention.

Abstract This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4–17) cm in length. After a mean follow-up of 71.84 (61–82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5–28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone.

ABSTRACT Background Ovarian cancer (OC) is an aggressive gynecological tumor usually diagnosed with malignant ascites and even observed widespread metastasis or distant spread. Aims We aimed to develop and identify radiomics models according to computed tomography (CT) for preoperative prediction of CXCL10 expression and prognosis in patients with OC. Methods Genomic data with CT images and corresponding clinicopathological parameters were extracted from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). To analyze the prognosis, we carried out the univariate Cox regression analysis (UCRA), multivariate Cox regression analysis (MCRA), and Kaplan–Meier (KM) analysis. For the data reduction, logistic regression, operator regression, least absolute shrinkage selection, radiomic feature construction, and feature selection were utilized. The predictive performance of the radiomic signatures was assessed using the analyses of the receiver operating characteristic (ROC) curve, decision curve (DCA), and precision‐recall (PR) curve. To evaluate the correlation between the radiomic score (Rad‐score) and CXCL10 expression, the Wilcoxon rank‐sum test was applied. Results Three radiomics models effectively predicted CXCL10 expression levels (AUC = 0.791, 0.748, and 0.718 for the set of training; AUC = 0.761, 0.746, and 0.701 for the set of validation). A higher Rad‐score significantly correlated with upregulated CXCL10 expression. Conclusion CXCL10 expression can be predicted noninvasively and preoperatively via radiomic signatures based on contrast‐enhanced CT images.

Recent research has highlighted the beneficial effects of urban green spaces on physical and mental health. This study focused on the hospital population and innovatively subdivided the population into four groups: doctors, caregivers, patients and nurses. A total of 96 volunteers participated in this virtual reality experiment to assess the restoration of a linear canopy landscape and a landscape with different levels of hydrodynamics through interactive audiovisual immersion. We utilized pre-research method, brainwave monitoring technique, psychological scales, observation and interviews in this experiment. The research identified five key findings. First, both linear canopy landscapes and those with low to medium hydrodynamic forces significantly enhance physiological and psychological restoration for all groups, with the most substantial physiological benefits observed in doctors and patients, and the greatest psychological relief noted in caregivers. Second, landscapes with medium hydrodynamic forces yield higher restorative effects than those with low forces in hospital settings. Third, green landscapes with medium and low-density canopies prove more conducive to patient recovery compared to those with high-density canopies. Fourth, the inclusion of bird songs does not markedly affect physiological restoration across the hospital groups. Finally, landscapes that incorporate elements of water dynamics, open skies, and lightly foliated canopies draw significant interest from all groups involved. This study advocates for the integration of natural blue and green elements into hospital environments as complementary therapeutic interventions, aiming to alleviate stress and promote health recovery among hospital communities.

At present, wireless power transfer (WPT) systems with constant current (CC) or constant voltage (CV) characteristics are typically achieved using a single transmitter and single pickup (STSP) configuration, which cannot transfer power to multiple battery loads simultaneously. In this paper, the LCC-LCC/S reconfigurable topology is proposed to realize the CC-to-CV transition for multiple battery loads. An LCC topology is designed on the primary side to achieve a constant current (0.362A) flowing through the transmitting coil to enable independent operation of power pickups. A reconfigurable LCC/S topology is designed on the secondary side to achieve the CC-to-CV transition of the battery loads. The received power from the pickups remains unaffected when pickups are moved in or out or are in different operating modes (CC or CV). The circuit can maintain zero phase angle (ZPA) operation, which greatly enhances the overall power density of the system. Additionally, detailed design process for the compensation parameters on both the primary and secondary sides are provided. Theoretical analysis proves that good system stability and robustness can be obtained in the case of variable quantity of pickups and quality factors of coils. The experimental prototype was built, with the CC value for the battery load designed at 0.7A and the CV value designed at 8 V. Experimental results demonstrate the smooth CC-to-CV transition of the proposed WPT system (with 3 pickups) at a power output of 15.4 W, and the system’s maximum efficiency can reach 75.5 %.

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

Abstract Vibration with a frequency of 100 Hz is widely distributed in the power equipment, and it can provide a new way to supply energy for sensors by vibration energy harvesting. The vibration energy harvesting method based on electromagnetic induction principle was studied through the arrayed structure of magnets and coils. Static magnetic field models were established for four magnet array structures and it was found that the alternating magnet array has the largest magnetic flux and magnetic flux gradient. Based on the alternating magnet array, prototypes of energy harvester with vertical and parallel movement mode were proposed. Through structural parameter optimisation analysis, two different energy harvesters were fabricated and it was found that the energy harvester with a parallel movement mode has better output performances. The energy harvester could provide output voltage/current and power of 8.35 V/17.39 mA and 15.13 mW (matched resistance is 200 Ω) at an acceleration of 5 m·s−2. The 100 mF capacitor could be charged to 2.72 V within 300 s, and the final voltage of the capacitor is greater than 3 V, which could sustainably drive commercial wireless temperature/humidity sensors.

Abstract Objective Autophagy‐related 5 (ATG5) facilitates the pathologic process of acute ischemic stroke (AIS) via multiple ways. This study aimed to identify the association of serum ATG5 with clinical outcomes in AIS patients. Methods Serum ATG5 from 280 AIS patients were detected at admission, Day (D)1, D3, D7, D30, and D90 after admission by enzyme‐linked immunosorbent assay. The median (interquartile range) follow‐up was 21.1 (5.9–43.9) months. Another 50 healthy controls (HCs) were also enrolled for serum ATG5 determination. Results ATG5 was elevated (p 2 and mRS ≤2 at D90, respectively. ATG5 at admission, D1, D3, D30, and D90 was elevated in AIS patients with mRS >2 versus those with mRS ≤2 (all p

Phosphorus (P) is essential for living plants, and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide. As the most important organ for plants, root morphology traits (RMTs) play a key role in P absorption. To investigate the genetic variability of RMT under low P availability, we dissected the genetic structure of RMTs by genome-wide association studies (GWAS), linkage mapping and candidate gene association studies (CGAS). A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions. The purple acid phosphatase gene BnPAP17 was found to control the lateral root number (LRN) and root dry weight (RDW) under low P stress. The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress. Moreover, the haplotype of BnPAP17Hap3 was detected for the selective breeding of P efficiency in oilseed rape. Over-expression of the BnPAP17Hap3 could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus (Po) utilization in oilseed rape. Collectively, these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.

Abstract Background Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. Methods In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. Results BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. Conclusions This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Background Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC.Methods The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan–Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-β-catenin signalling pathway.Results Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-β-catenin signalling pathway.Conclusions The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-β-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8−/− mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8+/+ mice, Irf8−/− mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI.

Cite this article: Bone Joint Res 2024;13(3):124–126.

The impact of COVID-19 on male reproductive function has been widely reported, but the underlying genetic basis of this relationship remains unclear. A new and useful method for exploring causal associations between exposures and outcomes is Mendelian randomization (MR), which utilizes genetic variants, also known as single nucleotide polymorphisms (SNPs), as instrumental variables (IVs) in a retrospective way. In this study, a two-sample MR analysis was conducted to investigate the potential causal effect of COVID-19 on male infertility using summary-level data from large-scale genome-wide association studies (GWAS). SNPs identified in the COVID-19 and male infertility GWAS were used as IVs, and the causal effect was estimated using three methods: inverse-variance weighted (IVW), weighted median, and MR-Egger regression. Additionally, a leave-one-out analysis was performed as a sensitivity analysis to assess the robustness of the findings. The exposures to COVID-19 were obtained from the largest and most recent GWAS, which included 9986 cases versus 1,877,672 controls for hospitalized patients and 5101 cases versus 1,383,241 controls of severe patients of European ancestry. The corresponding outcome for male infertility was also obtained from the largest and most recent GWAS meta-analysis of 680 cases and 72,799 controls of European ancestry. The results based on the three methods showed no significant association between hospitalized or severe COVID-19 and male infertility. Specifically, the odds ratio for IVW was 0.86 (95% confidence interval (CI): 0.65–1.15, p = 0.308), 0.96 (95% CI: 0.54–1.69, p = 0.886) for MR-Egger, and 0.87 (95% CI: 0.62–1.22, p = 0.430) for weighted median. These findings suggest that COVID-19 may have no causal effect on male reproductive function, although further studies are needed to validate these results. The present study provides evidence for a genetic association between COVID-19 (including both hospitalized and severe COVID-19) and male infertility.

Abstract Background Drought is one of the main consequences of global climate change and this problem is expected to intensify in the future. Resurrection plants evolved the ability to withstand the negative impact of long periods of almost complete desiccation and to recover at rewatering. In this respect, many physiological, transcriptomic, proteomic and genomic investigations have been performed in recent years, however, few epigenetic control studies have been performed on these valuable desiccation-tolerant plants so far. Results In the present study, for the first time for resurrection plants we provide evidences about the differential chromatin accessibility of Haberlea rhodopensis during desiccation stress by ATAC-seq (Assay for Transposase Accessible Chromatin with high-throughput sequencing). Based on gene similarity between species, we used the available genome of the closely related resurrection plant Dorcoceras hygrometricum to identify approximately nine hundred transposase hypersensitive sites (THSs) in H. rhodopensis. The majority of them corresponds to proximal and distal regulatory elements of different genes involved in photosynthesis, carbon metabolism, synthesis of secondary metabolites, cell signalling and transcriptional regulation, cell growth, cell wall, stomata conditioning, chaperons, oxidative stress, autophagy and others. Various types of binding motifs recognized by several families of transcription factors have been enriched from the THSs found in different stages of drought. Further, we used the previously published RNA-seq data from H. rhodopensis to evaluate the expression of transcription factors putatively interacting with the enriched motifs, and the potential correlation between the identified THS and the expression of their corresponding genes. Conclusions These results provide a blueprint for investigating the epigenetic regulation of desiccation tolerance in resurrection plant H. rhodopensis and comparative genomics between resurrection and non-resurrection species with available genome information.

We report a case of disseminated blue nevus-like melanoma with BRAF and CTNNB1 gene mutations. A 34-year-old man developed generalized blue-black maculopapules and nodules, sized 3-15 mm in diameters, all over the body, including the palms, soles, mucosa of the mouth and eyes for more than six months. The skin pathology showed a large number of epithelioid cells and melanin in the dermis, and immunohistochemistry showed positive for HMB-45, Mitf, SOX-10 (partially), Melan-A (slightly), S-100 (slightly) and Ki-67(about 10%). BRAF V600E (c1799T>A) and CTNNB1 T41I (c.122C>T) mutations were detected by tissue melanoma-related gene detection. Multiple liver nodules were found by PET-CT examination. The patient was diagnosed with disseminated blue nevus-like melanoma. After two months of treatment with dabrafenib mesylate and trametinib, the skin rashes became smaller and no new lesions were observed. Now the patient was lost to follow up.

Abstract Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it’s essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI. Graphical abstract

Abstract Background This study was designed to perform a comparative analysis between endoscopic ultrasonography (EUS) and double contrast-enhanced ultrasonography (DCEUS) for the preoperative diagnosis of gastric stromal tumors (GSTs). Methods A retrospective study was conducted involving 139 patients with histologically confirmed GSTs. All patients preoperatively underwent DCEUS and EUS. The pathology reports were treated as the baseline and were retrospectively compared with the findings of EUS and DCEUS. Results Of the 139 lesions, 120 and 113 were correctly identified by DCEUS and EUS, respectively, with an accuracy of 86.3% and 81.3%. The results revealed an insignificant difference between these two methods (p = 0.189). Conclusions DCEUS can display not only the locations, sizes, shapes, borders, internal echoes, but also show the blood perfusion patterns of GSTs. It is a highly accurate, noninvasive, and convenient method to be used at the pre-treatment stage.

Abstract Objective Haploinsufficiency is widely accepted as the pathogenic mechanism of hereditary spastic paraplegias type 4 (SPG4). However, there are some cases that cannot be explained by reduced function of the spastin protein encoded by SPAST. The aim of this study was to identify the causative variant of SPG4 in a large Chinese family and explore its pathological mechanism. Materials and methods A five-generation family with 49 members including nine affected (4 males and 5 females) and 40 unaffected individuals in Mongolian nationality was recruited. Whole exome sequencing was employed to investigate the genetic etiology. Western blotting and immunofluorescence were used to analyze the effects of the mutant proteins in vitro. Results A novel frameshift variant NM_014946.4: c.483_484delinsC (p.Val162Leufs*2) was identified in SPAST from a pedigree with SPG4. The variant segregated with the disease in the family and thus determined as the disease-causing variant. The c.483_484delinsC variant produced two truncated mutants (mutant M1 and M87 isoforms). They accumulated to a higher level and presented increased stability than their wild-type counterparts and may lost the microtubule severing activity. Conclusion SPAST mutations leading to premature stop codons do not always act through haploinsufficiency. The potential toxicity to the corticospinal tract caused by the intracellular accumulation of truncated spastin should be considered as the pathological mechanism of SPG4.

We selected 46 core winter–spring wheat cultivars from China’s main wheat-producing areas as experimental materials to clarify the differences in the physiological parameters of their cold resistance and provide a theoretical basis and high-quality germplasm for cold resistance breeding. We investigated differences in their cold resistance under field conditions for two consecutive years, and determined the physiological parameters of the cold resistance, yield, and quality indicators of different winter–spring wheat cultivars. Our results showed that the cold resistance of winter wheat cultivars was higher than that of spring wheat cultivars. The chlorophyll (Chl), soluble sugar (SS), soluble protein (SP), and free proline (Pro) contents of different winter–spring wheat cultivars were positively correlated with cold resistance, and malondialdehyde (MDA) content was negatively correlated with cold resistance. The five physiological parameters can be used as physiological indicators for the breeding of cold-resistant cultivars. The cold resistance, yield, and quality indicators of different spring and winter wheat cultivars were comprehensively evaluated by using the average membership value and comprehensive score. It was found that the average membership value and comprehensive score of winter wheat cultivars were higher than those of spring wheat cultivars. Through classification using the K-means method, the cold-resistant, high-yield, and high-quality cultivars were screened out, namely, Jimai23 (JM23), Jimai44 (JM44), Shannong57 (SN57), and Jinmai 919 (JM919).

Coal is an important fossil energy source in the world, which provides important support for the development of industry. However, the chemical composition of coal is complex, and it may cause harm to the human body and environment during the process of mining and utilization, especially some aromatic hydrocarbons in coal that are strongly carcinogenic to human beings; thus, it is necessary to analyze the organic chemical compositions of coal so as to realize the clean and harmless utilization of coal. In this article, three different coal samples were extracted by seven solvent-graded extractions, and then the extracts were tested by gas chromatography–mass spectrometry (GC-MS). According to the results of the GC-MS test, it was found that CS2 could dissolve a large amount of aromatic hydrocarbons in the coal, n-hexane could dissolve a larger amount of aliphatic hydrocarbons, methanol could dissolve a larger amount of ketones, benzene could extract phenolic compounds in the coal, acetone could dissolve alcoholic compounds, and the mixed solvent methanol/THF could dissolve coal esters. Then, by analyzing these extracts, researchers can clearly understand the microscopic organic components of coal, which have a significant role in the development of the coal chemical industry and ecological environment protection.

Background: To determine the effect of continuous care based on mobile application on patients' quality of life and self-care ability after mechanical heart valve replacement. Methods: Ninety patients who underwent cardiac mechanical valve replacement in the cardiovascular surgery department of a tertiary general hospital in Guizhou Province from September 2020 to January 2022 were selected for the study. The subjects were randomly divided into a control group and an intervention group using the SPSS25.0 software, with 45 patients in the two groups. The control group received routine nursing care during hospitalization, health education the day before discharge, and regular telephone and outpatient follow-up 6 months after discharge. Based on the control group's care, the intervention group received Mobile APP continuous care for 6 months. The effectiveness of patient's quality of life, medication adherence, international normalized ratio (INR) value compliance rates and self-care ability following mechanical heart valve replacement were evaluated the day before discharge and at the 1, 3 and 6 months after discharge. Results: Scores of quality of life, warfarin medication adherence, and self-care ability rose considerably in the intervention group compared to the control group, and the differences were statistically significant. Conclusion: The mobile phone application (APP) 's continuity of care could improve patients' quality of life, medication adherence, INR value compliance rates, and self-care ability. Clinical Trial Registration: No: ChiCTR2400081250. Registered 27 February, 2024, https://www.chictr.org.cn.

Metal based electroreflective devices (MERDs) have gained wide attention in recent years in the fields of smart windows and automotive glass due to their excellent photo-thermal modulation capability in the visible and near-infrared wavelength bands due to their high reflectivity. However, the high porosity due to the island-like growth of silver particles makes the devices susceptible to electrodeposited film breakage during prolonged energization or bleaching. This will seriously affect the effectiveness and stability of the device. In this paper, it is shown that the problem of Ag electrodeposition film fragmentation can be effectively overcome by replacing dimethyl sulfoxide solvent by N-methylpyrrolidone (NMP). The optical constants during film deposition were tested by the spectroscopic ellipsometry technique, and the porosity was calculated (reduced by 21.6%). The results show that MERDs with NMP as the solvent have more and more dispersed silver deposition sites, which leads to lower porosity of the silver deposited film during the deposition process. In addition, the lower turn-on voltage, greater contrast, longer memory effect, and greater coloring efficiency reveal that they are more promising for energy-saving applications.

IntroductionChronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD.MethodsTo eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses.ResultsThe gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism.DiscussionOur findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.

Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Abstract Objective In this study, we aimed to compare the outcomes of the two-stage induced membrane technique (IMT) and one-stage autografting in the treatment of aseptic atrophic nonunion in lower limb long bones. Methods From January 2014 to January 2022, we reviewed all surgically treated long bone nonunion patients, including patients aged 18 years or older with atrophic nonunion, who were either treated with the two-stage induced membrane technique (IMT) or one-stage autografting. Outcome parameters interns of clinical, quality of life and healthcare burden were recorded and retrospectively analysed between the two treatment populations. The follow-up time was at least 1 year. Results In total, 103 patients who met the criteria for aseptic atrophic nonunion were enrolled. Among them, 41 (39.8%) patients were treated with two-stage IMT, and 62 (60.2%) patients were treated with one-stage autologous bone grafting. The follow-up time was 12 to 68 months, with an average of 28.4 months. The bone healing rate was comparable in both groups (IMT: 92.7% vs. one-stage grafting: 91.9%, P = 0.089) at 12 months post-operation, and the bone healing Lane–Sandhu score was superior in the IMT group (mean: 8.68 vs. 7.81, P = 0.002). Meanwhile, the SF-12 scores of subjective physical component score (PCS) (mean: 21.36 vs. 49.64, P

Abstract Secukinumab is effective in treating patients with moderate‐to‐severe plaque psoriasis. However, most studies assessing its effectiveness in routine clinical settings in China are mostly single‐center studies with a limited sample size. The objective of this study was to assess secukinumab's efficacy, treatment patterns, and characteristics in patients with moderate‐to‐severe plaque psoriasis. This 24‐week, multicenter (n = 5) retrospective study analyzed the data of Chinese adult patients with moderate‐to‐severe plaque psoriasis who initiated secukinumab treatment between May 2019 and March 2020. The Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator's Global Assessment Modified 2011 (IGA mod 2011), and Dermatology Life Quality Index (DLQI) were assessed. Dermatologists documented the treatment dosage and modification reasons. Of the 244 secukinumab‐naïve patients, most were men (73.4%, 179/244) and weighed 60–90 kg (72.8%, 177/243). The mean (SD) age at secukinumab initiation was 38.1 (11.6) years, and the disease duration was 13.5 (7.9) years. Most patients (97.1%, 237/244) received secukinumab 300 mg. At weeks 4, 12, 16, and 24, the proportion of patients achieving PASI 75 (≥75% reduction from baseline) was 40.0%, 92.1%, 88.4%, and 88.9%, respectively; PASI 90 was 15.0%, 73.7%, 81.4%, and 68.3%, respectively; and PASI 100 was 8.7%, 40.8%, 58.1%, and 41.3%, respectively. During the same periods, BSA and IGA mod 2011 showed similar improvement trends. An increasing proportion of patients achieved DLQI of 0–1 (21.6%, 65.7%, 75.0%, and 80.3%, respectively). Treatment modification was highest at week 12. The average interval between two administrations after week 4 was 62.95 days. Secukinumab was highly effective in improving the PASI, IGA, BSA, and DLQI in Chinese patients with moderate‐to‐severe plaque psoriasis throughout the first 24 weeks. The treatment pattern for Chinese patients differs from that in the clinical guidelines.

Pumped-storage power stations (PSPSs) have higher requirements for anti-seepage compared with regular power stations. As a result, investigating the seepage distributions of PSPSs is particularly important. However, existing researches remain limited in assessing engineering needs such as ensuring the efficiency of a power station. Taking the Qingyuan PSPS as a typical case, this study aims to investigate the large-scale seepage field distribution while exploring the efficiency of the anti-seepage system. Considering the geological characteristics and structural location, a 3D finite element model is established. Based on the continuous medium model while combined with seepage control measures, the change in leakage while the anti-seepage system failed is further assessed. It is concluded that the operation status of anti-seepage measures will have a certain impact on the leakage volumes of each part. Using a comprehensive assessment, anti-seepage measures can effectively prevent seepage. When failure occurs on anti-seepage curtains, the leakage volume at the corresponding position will show an obvious growth. In summary, the findings of this study highlight the significance of avoiding excessive leakage caused by anti-seepage structure failure, the effective operation of anti-seepage measures must be ensured. The abovementioned results can provide scientific support for the seepage optimization design of PSPSs. HIGHLIGHTS The refined finite element model is established.; Based on the continuous medium model.; The distribution of the large-scale seepage field is analysed.; The leakage volume and external water pressure under different deployment schemes of seepage control measures are assessed.; A parameter sensitivity analysis of the curtain failure rate is carried out.;

Aims: This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. Methods: A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data. Results: After the screening, 44 studies were included with 1,079 patients and 1,083 segments of infected bone defects treated with the induced membrane technique. The mean defect size was 6.8 cm (0.5 to 30). After the index second stage procedure, 85% (797/942) of segments achieved union, and 92% (999/1,083) of segments achieved final healing. The multivariate analysis with data from 296 patients suggested that older age was associated with higher nonunion risk. Patients with external fixation in the second stage had a significantly higher risk of developing nonunion, increasing the need for additional procedures. The autografts harvested from the femur reamer-irrigator-aspirator increased nonunion, infection recurrence, and additional procedure rates. Conclusion: The induced membrane technique is an effective technique for treating infected bone defects. Internal fixation during the second stage might effectively promote bone healing and reduce additional procedures without increasing infection recurrence. Future studies should standardize individual patient data prospectively to facilitate research on the affected patient outcomes. Cite this article: Bone Joint Res 2023;12(9):546–558.

Background: The periosteum stem cells (PSCs) plays a critical role in bone regeneration and defect reconstruction. Insertion of polymethyl methacrylate (PMMA) bone cement can form an induced membrane(IM) and showed promising strategy for bone defect reconstruction, the underlying mechanism remains unclear. Our study sought to determine whether IM-derived cells(IMDCs) versus PSCs have similar characteristics in bone regeneration. Methods: IM and periosteum were harvested from ten bone defect patients treated with PMMA, the IMDCs and PSCs were isolated respectively. Morphological, functional and molecular evaluation was performed and matched for comparison. Results: Both progenitor-like IMDCs and PSCs were successfully isolated. In vitro, we found IMDCs were similar to PSCs in morphology, colony forming capacity and expression of surface marker(CD90+, CD73+, CD105+, CD34-/CD45-). Meanwhile, these IMSCs displayed multipotency with chondrogenic, adipogenic and osteogenic differentiation, but differed in some IMSCs(3/10) population showing relatively poor osteogenic differentiation. The molecular profiles suggests that cell cycle and DNA replication signaling pathways were associated with these varying osteogenic potential. In vivo, we established a cell-based tissue-engineered bone by seeding IMDSs/PSCs to demineralized bone matrix (DBM) scaffold and demonstrated both IMDSs and PSCs enhanced bone regeneration in SCID mice bone defect model compared with DBM alone. Conclusion: Our data demonstrated IM containing multipotent progenitor cells similar to that periosteum promoting bone regeneration, and indicated the existence of multiple subsets in osteogenic differentiation. Overall, the study provided a cellular and molecular insights in understanding the successful or failed outcome of bone defect healing.The translational potential of this article: This study confirmed IMDCs and PSCs share similar regeneration capacity and inform a translation potential of that cellular therapy applying IMDCs in bone defect repair.

Jiangsu is a province in China and has the highest frequency of tornado occurrences. Studying the meteorological background and mechanisms of tornado formation is crucial for predicting tornado events and preventing the resulting disasters. This paper analyzed the meteorological background, instability mechanisms, and lifting conditions of the two Enhanced Fujita Scale level 2 (EF2) and above tornadoes that occurred in southern Jiangsu on 14 May 2021 (“5.14”) and 6 July 2020 (“7.06”) using ERA5 reanalysis data. Detailed analyses of the internal structure of tornado storms were conducted using Changzhou and Qingpu radar data. The results showed that (1) both tornadoes occurred in warm and moist areas ahead of upper-level troughs with significant dry air transport following the cold troughs. The continuous strengthening of low-level warm and moist advection was crucial in maintaining potential instability and triggering tornado vortices. The 14 May tornado formed within a low-level shear line and a warm area of a surface trough, while the 6 July tornado occurred at the end of a low-level jet stream, north of the eastern section of a quasi-stationary front. (2) The convective available potential energy (CAPE) and K indices for both tornado processes were very close (391 for “5.14” and 378 for “7.06”), with the lifting condensation level (LCL) near the ground. The “5.14” showed greater instability and more favorable thermodynamic conditions, with deep southwesterly jets at the mid-level shear line producing rotation under strong convergent action (convergence center value exceeding −1 × 10−4s−1). In contrast, the “7.06” was driven by super-low-level jet stream pulsations and wind direction convergence under the influence of the Meiyu Front (convergence center value exceeding −1.5 × 10−4 s−1), resulting in intense lifting and vertical vorticity triggered by a surface convergence line. (3) The “5.14” tornado process involved a supercell storm over a surface dry line experiencing tilting due to strong vertical wind shear, which led to the formation of smaller cyclonic vortices near a hook echo that developed into a tornado. The “7.06” developed on a bow echo structure within a mesoscale convective system formed over the Meiyu Front, where dry air subsidence, entrainment, and convergence of the southeast jet stream triggered a “miniature” supercell. The relevant research results provide a reference for the prediction and early warning of tornadoes.

Utilization of large aggregates can promote energy conservation and emissions reductions, and large aggregates have been widely used in hydraulic concrete. The failure criterion for concrete material utilizing large aggregates forms the basis for constitutive models and structural design. However, the concrete failure criterion with respect to large aggregates has never been researched. To this end, the authors first conducted a series of triaxial compressive tests on concrete specimens with scaled aggregates. On this basis, several 3D mesoscopic numerical models were established with different aggregate gradations and used to simulate the triaxial compressive behaviors of hydraulic concrete after the models had been verified by experimental results. The results showed a pronounced aggregate-gradation effect on triaxial compressive behaviors, and concrete mixes with larger aggregates usually have higher compressive strength, especially under conditions of higher confinement. The normalized peak strength can increase by up to 23.49%. Finally, based on the available testing data, the strength criterion in different constitutive models is discussed and modified to allow more accurate simulation of the dynamic responses of and damage to fully graded concrete structures. This result can provide a theoretical basis on which construction entities can optimize the mix proportions of fully graded concrete and detect the failure modes of concrete structures.

Aims: This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods: We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results: In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months’ (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion: Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence. Cite this article: Bone Joint Res 2023;12(8):467–475.

According to the variable toe-to-heel well spacing, combined with the dislocation theory, discrete lattice method, and finite-element-method (FEM) based fluid-solid coupling, an integrated geological-engineering method of volume fracturing for fan-shaped well pattern is proposed considering the geomechanical modeling, induced stress calculation, hydraulic fracturing simulation, and post-frac productivity evaluation. Besides, we propose the differential fracturing design for the conventional productivity-area and the potential production area for fan-shaped horizontal wells. After the fracturing of the conventional production area for H1 fan-shaped well platform, the research shows that the maximum reduction of the horizontal principal stress difference in the potential productivity-area is 0.2 MPa, which cannot cause the stress reversal, but this reduction is still conducive to the lateral propagation of hydraulic fractures. According to the optimized fracturing design, in zone-I of the potential production area, only Well 2 is fractured, with a cluster spacing of 30 m and an injection rate of 12 m3/min per stage; in zone-II, Well 2 is fractured before Well 3, with a cluster spacing of 30 m and an injection rate of 12 m3/min per stage. The swept area of the pore pressure drop in the potential production area is small, showing that the reservoir is not well developed. The hydraulic fracturing in the toe area can be improved by, for example, properly densifying the fractures and adjusting the fracture distribution, in order to enhance the swept volume and increase the reservoir utilization.

Abstract Background Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear. Methods Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups. Results (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF. Conclusion (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Abstract Introduction The weight-adjusted-waist Index (WWI), an innovative metric for assessing obesity, exhibits superior efficacy in appraising lean muscle and adipose tissue mass relative to both the Body Mass Index (BMI) and Waist Circumference (WC). The objective of this research paper is to investigate the correlation between WWI and the incidence of Rheumatoid Arthritis (RA) and Osteoarthritis (OA). Methods In this population-based study, we collected data from adult participants aged 20–80 years using the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2020 to analyze the association between WWI and the occurrence of RA and OA. NHANES, a nationally representative cross-sectional survey, is designed to evaluate the health and nutritional status of the U.S. population. The current research incorporates an extensive, nationally representative sample of U.S. adults, utilizing weighted multivariate linear regression and smoothed curve fitting techniques to examine linear and non-linear relationships. Threshold effects were determined through a two-part linear regression model. Additionally, subgroup analyses and interaction tests were conducted to explore the connection between WWI and the incidence of RA and OA. Results Our findings reveal a linear positive correlation between WWI and OA prevalence, indicating that an increase in WWI is linked to a heightened risk of OA. Conversely, a non-linear relationship was observed between WWI and RA prevalence, exhibiting a significant threshold effect with a saturation value of 11.21 cm/√kg. A positive association was detected to the left of the saturation point, while no significant association was present between the two variables to the right of the saturation point, suggesting a complex non-linear relationship between RA prevalence and WWI. Conclusions This investigation demonstrates a positive linear association between WWI and OA prevalence, as well as a complex non-linear relationship with RA prevalence in U.S. adults aged 20–80 years.

Abstract The conversion of lignocellulosic feedstocks to fermentable sugar for biofuel production is inefficient, and most strategies to enhance efficiency directly target lignin biosynthesis, with associated negative growth impacts. Here we demonstrate, for both laboratory- and field-grown plants, that expression of Pag-miR408 in poplar (Populus alba × P. glandulosa) significantly enhances saccharification, with no requirement for acid-pretreatment, while promoting plant growth. The overexpression plants show increased accessibility of cell walls to cellulase and scaffoldin cellulose-binding modules. Conversely, Pag-miR408 loss-of-function poplar shows decreased cell wall accessibility. Overexpression of Pag-miR408 targets three Pag-LACCASES, delays lignification, and modestly reduces lignin content, S/G ratio and degree of lignin polymerization. Meanwhile, the LACCASE loss of function mutants exhibit significantly increased growth and cell wall accessibility in xylem. Our study shows how Pag-miR408 regulates lignification and secondary growth, and suggest an effective approach towards enhancing biomass yield and saccharification efficiency in a major bioenergy crop.

Abstract Keratinocyte hyperproliferation is a key pathogenic factor in psoriasis. However, the mechanisms that regulate keratinocyte hyperproliferation in this condition remain unclear. Here, we found that SLC35E1 was highly expressed in keratinocytes of patients with psoriasis and that Slc35e1 −/− mice displayed a less severe imiquimod (IMQ)-induced psoriasis-like phenotype than their wild-type siblings. In addition, SLC35E1 deficiency inhibited keratinocyte proliferation in both mice and cultured cells. On a molecular level, SLC35E1 was found to regulate zinc ion concentrations and subcellular localization, while zinc ion chelation reversed the IMQ-induced psoriatic phenotype in Slc35e1 −/− mice. Meanwhile, epidermal zinc ion levels were decreased in patients with psoriasis and zinc ion supplementation alleviated the psoriatic phenotype in an IMQ-induced mouse model of psoriasis. Our results indicated that SLC35E1 can promote keratinocyte proliferation by regulating zinc ion homeostasis and zinc ion supplementation has potential as a therapy for psoriasis.

Abstract This paper proposes a novel cubic WPT system for an enclosed sensor scenario, and its transmission characteristics in a metal environment have been analyzed. In addition, stable and high transmission efficiency can be normally achieved in all positions. The proposed quasi‐double D coil structure is composed of two pairs of transmitting coils; each transmitting coil pair is placed face to face and connected serially. Through current amplitude modulation, magnetic flux can flow towards the centre of the receiving coil and keep the system high efficiency when the rotation angle of the receiving coil changes. However, the installation position of the receiving coil is not fixed in the switch cabinet application, and an irregular iron wall and the metal shell of sensors could also lead to inconsistent iron loss of multiple transmitters. To overcome the resulting disturbances in efficiency, the improved current amplitude control method and the optimal load have been theoretically deduced in the case of the position variation of the receiving coil in a metal environment. Finally, experimental results in two‐dimensional space verify the omnidirectional transmission capability of the proposed quasi‐double D coil, and efficiency disturbances are effectively alleviated.

IntroductionNeuropathic Pain (NP) is often accompanied by mood disorders, which seriously affect the quality of life of patients. This study aimed to analyze the hotspots and trends in NP-related mood disorder research using bibliometric methods and to provide valuable predictions for future research in this field.MethodsArticles and review articles on NP-related mood disorders published from January 2003 to May 2023 were retrieved from the Web of Science Core Collection. We used CiteSpace to analyze publications, countries, institutions, authors, cited authors, journals, cited journals, references, cited references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps.ResultsA total of 4,540 studies were collected for analysis. The number of publications concerning NP-related mood disorders every year shows an upward trend. The United States was a major contributor in this field. The University of Toronto was the most productive core institution. C GHELARDINI was the most prolific author, and RH DWORKIN was the most frequently cited author. PAIN was identified as the journal with the highest productivity and citation rate. The current research hotspots mainly included quality of life, efficacy, double-blind methodology, gabapentin, pregabalin, postherpetic neuralgia, and central sensitization. The frontiers in research mainly focused on the mechanisms associated with microglia activation, oxidative stress, neuroinflammation, and NP-related mood disorders.DiscussionIn conclusion, the present study provided insight into the current state and trends in NP-related mood disorder research over the past 20 years. Consequently, researchers will be able to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.

This study explored the effect of individualised nutritional intervention on the postpartum nutritional status of patients with the growth and development of their offspring. This study included pregnant women with gestational diabetes mellitus (GDM) at Hangzhou Women’s Hospital in 2019. At 42 days after childbirth, the HbA1c (95% CI: 0.44-0.56%, p 0.05). There were significant differences in the number of macrosomia and neonatal weight between the two groups (both p 0.05). Individualised nutritional intervention could improve blood glucose levels 42 days after childbirth and reduce macrosomia incidence in pregnant women with GDM.Impact statement What is already known on this subject? Individualised nutrition intervention can improve blood glucose status and complications during pregnancy, thus improving pregnancy outcomes. What the results of this study add? Individual nutrition intervention improved the blood glucose and nutritional status of patients at 42 days postpartum, but there was no difference in the growth and development indicators of their offspring at 0–24 months. What the implications are of these findings for clinical practice and/or further research? Improve nutritional intervention programs for gestational diabetes, improve blood glucose during pregnancy and postpartum, to improve pregnancy outcomes and reduce the occurrence of type 2 diabetes and other metabolic diseases; Extend the monitoring range of the growth and development of the offspring of gestational diabetes, find the problems and timely carry out the nutritional intervention, to improve the development of the offspring.

Abstract This study was designed to evaluate the impact of methicillin resistance on the outcomes among patients with S. aureus osteomyelitis. We reviewed all extremity osteomyelitis patients treated in our clinic center between 2013 and 2020. All adult patients with S. aureus pathogen infection were included. Clinical outcome in terms of infection control, length of hospital stay, and complications were observed at the end of a 24‐month follow‐up and retrospectively analyzed between populations with/without methicillin resistance. In total, 482 osteomyelitis patients due to S. aureus were enrolled. The proportion of methicillin-resistant S. aureus (MRSA) was 17% (82) and 83% (400) of patients had Methicillin-sensitive S. aureus (MSSA). Of 482 patients, 13.7% (66) presented with infection persistence after initial debridement and antibiotic treatment (6 weeks), needed repeated debridement, 8.5% (41) had recurrence after all treatment end and a period infection cure, complications were observed in 17 (3.5%) patients (pathologic fracture; 4, nonunion; 5, amputation; 8) at final follow-up. Following multivariate analysis, we found patients with S. aureus osteomyelitis due to MRSA are more likely to develop a persistent infection (OR: 2.26; 95% CI 1.24–4.13) compared to patients with MSSA. Patients infected with MRSA also suffered more complications (8.5% vs. 2.5%, p = 0.015) and longer hospital stays (median: 32 vs. 23 days, p

Objective To investigate the influence of mild psoriasis on the quality of patients' lives. Methods Based on PASI score and quality of life index, a questionnaire was designed to investigate the quality of lives in aspects of physiology, psychology, daily life, social entertainment, family, work and study in 95 patients with mild plaque psoriasis, aged 18~65 years. Logistic regression was used to analyze the quality of life-related factors. Results The quality of lives of 45 patients (47.37%) was affected by psoriasis. Moreover, an increase in one PASI score increased the risk of affecting quality of lives to 1.291 times, while an increase in one PGA score increased the risk of affecting quality of lives to 3.574 times. Conclusion Mild plaque psoriasis can affect the quality of patients′ lives to some extent.

Background Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD. Methods We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells. Results In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells. Conclusion Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.