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[Display omitted] • It was firstly demonstrated that the synergistic activation of PMS by MoS 2 @PANI and Cu(II). • High removal rate of sulfathiazole (≥85 %) achieved within a wide range of pH (3–10) in Cu(II)/MoS 2 @PANI/PMS. • H O ∙ , Cu(Ⅲ) and 1 O 2 were generated in Cu(II)/MoS 2 @PANI/PMS, while SO 4 ∙ - was negligible. • Compared with Fe(II), Cu(II) improved reusability and applicability of MoS 2 @PANI in activation of PMS. • The absorption of Cu(II) on MoS 2 @PANI improved the stability of MoS 2 @PANI. This paper synergistically combined MoS 2 @PANI (coating MoS 2 on polyaniline (PANI)) with Cu(II) to obtain effective activation of PMS in a wide range of pH (3–10). The removal rate of sulfathiazole (ST) in Cu(II)/MoS 2 @PANI/PMS (98 %) in 60 min was higher than in Cu(II)/PMS (50 %) and MoS 2 @PANI/PMS (70 %). Besides, the PMS consumption rate was 100 % within 30 min in Cu(II)/MoS 2 @PANI/PMS. Different concentrations of Cl - and HCO 3 - promoted the degradation of ST in varying degrees. And NO 3 - slightly inhibited the degradation of ST (removal rate more than 84 %). Notably, Cu(II)/MoS 2 @PANI/PMS could remove more than 80 % ST in different water bodies. The special structure of MoS 2 @PANI increased many activity sites of Mo(IV) to promote the cycle of Cu(II)/Cu(I) for activating PMS which generated H O ∙ , Cu(III) and 1 O 2. Twenty-seven degradation intermediates were identified and four possible degradation paths of ST were proposed. Moreover, Cu(II)/MoS 2 @PANI/PMS possessed a good non-selectivity for various organic pollutants. After three consecutive cycles, the removal rate still retained more than 90 % in Cu(II)/MoS 2 @PANI/PMS system. Compared with Fe(II), MoS 2 @PANI was more stable in Cu(II)/MoS 2 @PANI/PMS. The synergy of Cu and Mo broke the limitation of PMS activation under environmental aquatic conditions. Given that Cu(II) widely existed in wastewater, the new research strategy increased the application scope for homogeneous PMS activation with inherently Cu(II) in wastewater in environmental remediation. [ABSTRACT FROM AUTHOR]

This research focuses on the bias and type I error control issues when the marginal structural models (MSMs) are applied to evaluate the causal survival benefits of active intervention versus control in randomized clinical trials (RCTs) with treatment switching after disease progression. When MSMs are applied in the RCT setting, the question of interest, model specifications, strategies for type I error control, bias reduction, etc. differ somewhat from those for observational studies. This manuscript discusses the approaches used to accommodate these differences. Through Monte Carlo simulations and a case study, our research demonstrates that, with sufficient attention paid to issues applicable to RCTs in particular, MSMs may perform better than the inverse probability of censoring weighting (IPCW) method in analyzing the survival endpoint in RCTs with treatment switching because more information is used by the MSM. [ABSTRACT FROM AUTHOR]

Background: Ethnic Koreans in China are a distinct minority group. Highly educated populations are at high risk of depression. The aim of this study was to explore the associations of depression and metabolic syndrome (MS) in highly educated ethnic Koreans in China, and determine whether the associations were dependent on gender. Methods: From March 11th to 27th 2017, the natural population of 18– 70 year olds was continuously screened at Yanbian Korean Autonomous Region. Those who met the inclusion criteria were invited to complete Zung Self-Rating Depression Scale (SDS). The people with SDS > 53 were assigned to depression group and those with SDS ≤ 53 were assigned to the control group. Demographic characteristics, clinical factors, life-style factors and family history were collected and compared. Besides, associations of depression with MS and its components were estimated by Spearman correlation analysis and logistic regression analysis. Results: The depression group included 367 highly educated ethnic Koreans with depression status and the control group consisted of 388 age-, education-, and gender-matched ethnic Koreans without depression. A significantly higher prevalence of MS was observed in males and females with depression status relative to the control subjects (males, 28.5% vs 6.3%, X2 = 16.162, P-value < 0.001; females, 33.0% vs 7.5%, X2 = 57.896, P-value < 0.001). Depression status was positively correlated with MS in males (r = 0.311, P-value < 0.01) and females (r = 0.332, P-value < 0.01). After adjusting for potential confounding factors, mild and moderate depression statuses were found to be significantly associated with MS development in male and female ethnic Koreans, respectively. Conclusion: Our findings suggest a close link between depression and MS independent of gender in highly educated ethnic Koreans of China. [ABSTRACT FROM AUTHOR]

It is important to further improve the electrophysiology and electrochemistry techniques of neurotransmitter detection. Here, we report the development of multifunctional nanopipette-based integrated approaches for the detection of neurotransmitters. We successfully fabricated a nanopipette with two independent functional units at the apex, a nanopore and a gold nanoelectrode (GNE). The GNE shows good electrochemical response to dopamine (DA). Furthermore, both the nanopore and nanoelectrode can effectively enrich DA but not ascorbic acid by electrical means. The enriched DA is then detected and analysed with an obviously improved signal-to-noise ratio by electrochemical methods and surface-enhanced Raman spectroscopy (SERS). In addition, with the addition of silver nanoparticles during enrichment, up to 10 times increase of the Raman intensity of DA can be observed. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) has a high prevalence in female patients and sex may be a key factor affecting the progression of OA. The aim of the present study was to identify genetic signatures in the synovial membranes of female patients with OA and to elucidate the potential associated molecular mechanisms. The gene expression profiles of the GSE55457 and GSE55584 datasets were obtained from the Gene Expression Omnibus database. Data of two synovial membranes from normal female individuals (GSM1337306 and GSM1337310) and two synovial membranes from female patients affected by OA (GSM1337327 and GSM1337330) were obtained from the dataset GSE55457, and those of three synovial membranes from female patients affected by OA (GSM1339628, GSM1339629 and GSM1339632) were obtained from the dataset GSE55584. Differentially expressed genes (DEGs) were identified by using Morpheus software. Protein‑protein interaction (PPI) networks of the DEGs were constructed by using Cytoscape software. Subsequently, Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of the top module of the PPI network were performed by using ClueGo. A total of 377 DEGs were identified in the synovial membranes of OA patients compared with those of normal individuals, including 164 upregulated and 213 downregulated genes. The top 10 hub genes were ubiquitin (UB)C, ribosomal protein (RP) L23A, mammalian target of rapamycin, heat shock protein 90 α family class A member 1, RPS28, RPL37A, RPS24, RPS4X, RPS18 and UBB. The results of the GO analysis indicated that the DEGs included in the top module of the PPI were mainly enriched in the terms ‘nuclear‑transcribed mRNA catabolic process’, ‘nonsense mediated decay’, and ‘cytoplasmic translation and ribosomal small subunit biogenesis’. KEGG pathway analysis indicated that the DEGs included in the top one module were mainly enriched in the ‘ribosome’ pathway. The present study provides a systematic, molecular‑level understanding of the degeneration of the synovial membrane in the progression of OA in female patients. The hub genes and molecules associated with the synovial membrane may be used as biomarkers and therapeutic targets for the treatment of OA in female patients with OA. [ABSTRACT FROM AUTHOR]

[Display omitted] • The MoS 2 @PANI/PMS with trace Fe(II) system degraded nearly 100 % of TAP in 15 min. • The cycle of Fe(III)/Fe(II) was greatly accelerated by MoS 2 @PANI. • The degradation of TAP was effective in a wide pH range of 3 to 9. • SO 4 · - , H O · , O 2 · - and 1O 2 were identified in the Fe(II)/MoS 2 @PANI/PMS system. • Possible degradation pathways and product toxicity of TAP were proposed. Fe(II) displayed a great potential in peroxymonosulfate (PMS) activation to remove pollutants but was limited by the cycle of Fe(III)/Fe(II) in the process. To solve this problem, different percentages of flower-like MoS 2 nanosheets were successfully coated on the surface of polyaniline (PANI) nanotubes named as MoS 2 @PANI-X(1, 2, 3) activating PMS efficiently with trace Fe(II) to remove thiamphenicol (TAP), in which MoS 2 @PANI-2 with 92.6% of MoS 2 was the best by removing 99% TAP within 15 min. Notably, the used trace Fe(II) concentration (2 μM) was environmentally friendly because it was far lower than the allowable limit (0.3 mg/L) in standard for drinking water by WHO. With the increase of PMS concentration (0.1–2.0 mM), k PMS increased from 0.083 to 0.118 min−1 and then decreased to 0.098 min−1.When MoS 2 @PANI-2 dosage increased from 10 to 50 mg/L, k M o S 2 @ P A N I - 2 increased from 0.068 to 0.558 min−1. However, N O 3 - , C l - , H P O 4 2 - , H C O 3 - , H 2 P O 4 - and natural organic matter inhibited the degradation of TAP in varying degrees. The special structure of MoS 2 @PANI increased many activity sites of Mo(IV) to promote the cycle of Fe(III)/Fe(II) for sustainable and effective activating PMS which generated SO 4 · - , H O · , O 2 · - and 1O 2 to achieve high removal rate of TAP in a wide range of pH (3–9) (>93%). Twenty-two degradation intermediates were identified and three possible degradation paths of TAP were proposed. Overall, this study provided a novel strategy to remove antibiotics by overcoming the limiting cycle of Fe(III)/Fe(II) in the peroxymonosulfate activation process, which had a great application in water treatment. [ABSTRACT FROM AUTHOR]

Purpose: Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). Methods: In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. Results: In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. Conclusion: We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD. [ABSTRACT FROM AUTHOR]

Background: The purpose of this meta-analysis was to compare the blood loss and complications of intra-articular (IA) with intravenous (IV) tranexamic acid (TXA) for total knee arthroplasty (TKA).Methods: A comprehensive search of studies was conducted to identify related articles in Pubmed, Embase, Cochrane central Register of Controlled Trials, springerLink, OVID and the Research published from January 1980 to September 2016. All studies that compared IA TXA with IV TXA application on TKA were included. Main outcomes of the two methods were collected and analyzed by using Review Manager 5.3.Results: There were 16 randomized controlled trials with 1308 cases met the criteria. Compared with IV TXA, IA TXA had similar blood volume of drainage, hidden blood loss, transfusion rate and complications (P > 0.05). IA TXA had lower total blood loss than IV TXA, and there was significant difference (P < 0.05). Subgroup analysis of total blood loss based on times of IV TXA administration showed that repeat dose of IV TXA had a higher total blood loss and postoperative hemoglobin drop (P < 0.05) than IA TXA. However, single dose of IV TXA had a similar efficacy on total blood loss and postoperative hemoglobin drop (P > 0.05) when compared with IA TXA.Conclusions: Both IA TXA and single dose of IV TXA are effective in reducing total blood loss and postoperative hemoglobin drop without increasing complications of DVT or PE. The current meta-analysis suggests that 1.5 g TXA by IA administration or 1 g TXA by IV administration 10 min before tourniquet deflation is effective and safe in patients undergoing TKA. [ABSTRACT FROM AUTHOR]

Background/Aims: Since renal fibrosis always predisposes end-stage renal disease, elucidation of the molecular mechanisms that underlie the progression of renal fibrosis may substantially improve the understanding and treatment for renal failure. Previous studies have highlighted an important counteraction between transforming growth factor β 1 (TGFβ1) and bone morphogenic protein 7 (BMP7) in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells during chronic renal injury. Macrophages are also believed to play a critical role in renal fibrosis. However, the relationship between macrophages and EMT is unknown. Methods: Here, we used a mouse unilateral ureteral obstruction (UUO) model to address to these questions, and analyzed macrophage and its subpopulations purified by flow cytometry. Results: We found that the recruited macrophages are polarized to a M2 subtype after renal injury. M2 macrophages released high levels TGFβ1 to suppress BMP7 to enhance EMT-induced renal fibrosis. Depletion of M2 macrophages, but not of M1 macrophages, specifically inhibited EMT, and subsequently the renal fibrosis. Adoptive transplantation of M2 macrophages deteriorated renal fibrosis. Conclusion: Thus, our study highlights M2 macrophages as a critical target for treating renal fibrosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective Oxidants play an important role in many diseases, including hearing loss. We hypothesized that (-)-epigallocatechin-3-gallate (EGCG) would protect spiral ganglion cells (SGCs) from H 2 O 2 -induced oxidizing damage. Material and Methods SGCs of postnatal day 1-3 mice were cultured in vitro. H 2 O 2 and EGCG were used at various concentrations. The apoptotic rate of SGCs was evaluated using Hoechst 33 258 staining, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. Semi-quantitative reverse transcriptase polymerase chain reaction was used to observe manganese superoxide dismutase (MnSOD) gene expression of SGCs treated with H 2 O 2 and EGCG. Results The viability of cultured SGCs was significantly decreased, and the apoptotic rate of SGCs significantly increased, at H 2 O 2 concentrations ≥50 μM compared with the control ( p <0.05). MnSOD gene expression was upregulated with increasing H 2 O 2 concentration in cultured SGCs, while this upregulation was suppressed by EGCG. Conclusion It is suggested that EGCG, as an antioxidant, significantly protects auditory neurons against H 2 O 2 -induced oxidative damage. [ABSTRACT FROM AUTHOR]

[Display omitted] • We developed SPEEK@PDA-LAP to regulate macrophage-mediated bone homeostasis. • SPEEK@PDA-LAP alleviated intracellular ROS accumulation and further inhibited the NLRP3 inflammasome-mediated pyroptosis in macrophages. • The inhibition effect of ROS/NLRP3/IL-1β-mediated pyroptosis contributes to the restoration of the balance between osteogenesis and osteoclastogenesis in vitro and in vivo. The treatment of osteoporotic implant failures tends to be challenging due to an imbalance in bone homeostasis. Recently, the accumulation of intracellular reactive oxygen species (ROS) and activation of the inflammasome containing nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) protein have been shown to indirectly affect osteogenesis and osteoclastogenesis. Owing to the release of multi-metal ions from laponite (LAP), we fabricated a multifunctional LAP coating on a three-dimensional microporous sulfonated polyetheretherketone (SPEEK) surface via polydopamine (PDA) modification (SPEEK@PDA-LAP). The balance between osteogenesis and osteoclastogenesis was examined using macrophages in an osteo-immune microenvironment. Employing in vitro assays, we showed that the SPEEK@PDA-LAP alleviated intracellular ROS accumulation and inhibited the activation of NLRP3 inflammasome-mediated pyroptosis in macrophages, creating an osteoimmunomodulatory microenvironment to stimulate osteogenesis and inhibit osteoclastogenesis. The micro-computed tomography and histological results of in vivo experiments indicated that SPEEK@PDA-LAP implants reversed the balance between osteogenesis and osteoclastogenesis to promote the formation of new bone around the implant even under osteoporotic conditions. The results indicate that inhibiting the NLRP3 inflammasome and regulating intracellular ROS in macrophages can be an effective therapy for osteoporosis. These results highlight the potential of functional PEEK materials for bone regeneration in patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Tissue defect is one of the significant challenges encountered in clinical practice. Nanomaterials, including nanoparticles, nanofibers, and metal-organic frameworks, have demonstrated an extensive potential in tissue regeneration, offering a promising avenue for future clinical applications. Nonetheless, the intricate landscape of the inflammatory tissue microenvironment has engendered challenges to the efficacy of nanomaterial-based therapies. This quandary has spurred researchers to pivot towards advanced nanotechnological remedies for overcoming these therapeutic constraints. Among these solutions, microenvironment-sensitive nanozymes have emerged as a compelling instrument with the capacity to reshape the tissue microenvironment and enhance the intricate process of tissue regeneration. In this review, we summarize the microenvironmental characteristics of damaged tissues, offer insights into the rationale guiding the design and engineering of microenvironment-sensitive nanozymes, and explore the underlying mechanisms that underpin these nanozymes' responsiveness. This analysis includes their roles in orchestrating cellular signaling, modulating immune responses, and promoting the delicate process of tissue remodeling. Furthermore, we discuss the diverse applications of microenvironment-sensitive nanozymes in tissue regeneration, including bone, soft tissue, and cartilage regeneration. Finally, we shed our sights on envisioning the forthcoming milestones in this field, prospecting a future where microenvironment-sensitive nanozymes contribute significantly to the development of tissue regeneration and improved clinical outcomes. This review article highlights recent representative research progresses using microenvironment-sensitive nanozymes for enhancing tissue regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the most common cause of death globally. In which atrioventricular block (AVB) is a common disorder with genetic causes, but the responsible genes have not been fully identified yet. To determine the underlying causative genes involved in cardiac AVB, here we report a three-generation Chinese family with severe autosomal dominant cardiac AVB that has been ruled out as being caused by known genes mutations. Whole-exome sequencing was performed in five affected family members across three generations, and co-segregation analysis was validated on other members of this family. Whole-exome sequencing and subsequent co-segregation validation identified a novel germline heterozygous point missense mutation, c.49287C > A (p.N16429K), in the titin (TTN , NM_001267550.2) gene in all 5 affected family members but not in the unaffected family members, neither in the large population according to the Genome Aggregation Database (https://gnomad.broadinstitute.org/). The point mutation is predicted to be functionally deleterious by in - silico software tools. Our finding was further supported by the conservative analysis across species. Based on this study, TTN was identified as a potential novel candidate gene for autosomal dominant AVB; this study expands the mutational spectrum of TTN gene and is the first to implicate TTN mutations as AVB disease causing in a Chinese pedigree. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) exhibit exceptional characteristics, including high porosity and adjustable properties, rendering them highly suitable for biomedical applications. Recently, researchers have directed their attention toward the integration of MOFs into composites for bone tissue regeneration (BTE), presenting distinct advantages over conventional substitutes. In this comprehensive review, the authors delve into the latest advancements concerning MOF‐integrated composites for BTE. This exploration encompasses an examination of the properties of MOFs and the various synthesis techniques employed to fabricate these materials. Furthermore, the diverse applications of MOF‐integrated composites in BTE are investigated, encompassing areas such as antibacterial properties, osteogenic differentiation, angiogenesis, and immunomodulation. By providing a comprehensive overview of the ongoing research on MOF‐integrated composites for BTE, this study holds the promise of yielding innovative solutions within the realm of orthopedics. [ABSTRACT FROM AUTHOR]

Objective. To discuss the changes in the quality of life, psychological status, medication compliance, and prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by applying plan-do-check-action (PDCA) cycle management model. Methods. A total of 125 patients with AMI who underwent PCI in our hospital from June 2018 to June 2020 were selected and divided into control group (n = 62) and research group (n = 63) by the random number method. The conventional nursing measures were used in the control group, and the PDCA cycle management model on the basis of the control group was used in the research group. The changes in the quality of life, psychological status, medication compliance, and prognosis were observed. Results. After intervention, the Generic Quality of Life Inventory-74 scores and the self-made medication compliance questionnaire score of the research group were higher than the control group (P < 0.05). After intervention, the self-rating anxiety scale score and self-rating depression scale score of the research group were lower than those of the control group (P < 0.05). The total incidence of adverse events in the research group (7.94%) was lower than that in the control group (20.97%) (P < 0.05). Conclusion. After the application of PDCA cycle management model, the quality of life, psychological status, medication compliance, and prognosis of AMI patients who underwent PCI were improved. [ABSTRACT FROM AUTHOR]

Guanine (G) oxidation products, such as 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-oxo-guanine (8-OXOG), have been widely studied as promising biomarkers for DNA oxidative damage. In this work, we develop a new method to detect G oxidative products released from live cells after chromium (VI) ion or hydrogen peroxide treatments by using a glass nanopipette-based flexible gold nanoelectrode (fGNE). Specific response to G oxidative products with high sensitivity can be detected from the fGNE tip through integrated electrochemical measurements and surface-enhanced Raman spectroscopy. The fGNE apex can be positioned very close to the cell membrane noninvasively because of its high flexibility and nanoscale tip size. With the assistance of the electrophoretic force, the fGNEs can effectively collect and detect the G-derived DNA damage products released from individual cells in the cell culture medium with high sensitivity. [ABSTRACT FROM AUTHOR]

The drug‐resistant bacterial‐infected skin wound is still a severe healthcare problem. Uncontrolled bacterial infection, abundant reactive oxygen species (ROS) content, and prolonged inflammatory response are detrimental to wound healing. Moreover, excessive vessel growth can result in unsatisfactory scar formation. Herein, a three‐step regenerative strategy based on a bilayered gelatin/acryloyl β‐cyclodextrin (BGACD) hydrogel containing physical host–guest complexations and chemical crosslinks is proposed. The hydrogel is loaded with humic acids (HAs) and astragaloside IV (AS) in the lower layer and verteporfin (Vt) in the upper layer. Different gelatin/acryloyl β‐cyclodextrin ratios endow the lower and upper layers of the hydrogel with different degradation rates. Under light irradiation, the combination of HAs‐induced photothermal therapy (PTT) and verteporfin‐induced photodynamic therapy effectively inhibits MRSA growth. The HAs and astragaloside IV are released from the lower layer to scavenge ROS and promote M2 macrophage polarization and angiogenesis during the inflammation and early proliferation phases, while verteporfin releases from the upper layer suppress excessive vessel growth during the late proliferation and remodeling phases. The HAs‐AS@Vt@BGACD hydrogel successfully achieves rapid and scarless wound healing in an MRSA‐infected wound model in rats. Therefore, the HAs‐AS@Vt@BGACD hydrogel shows promising potential for the treatment of drug‐resistant bacteria‐infected skin wound healing. [ABSTRACT FROM AUTHOR]

The modification of substrate concentration and acidification level in inoculum treatment can significantly enhance hydrogen production while reducing costs. Hydrogen production showed a significant variation with food waste (FW) concentration, ranging from 10 to 120 gVS/L. Insufficient acidity at lower FW concentrations of 10, 20, and 40 gVS/L limited hydrogen production to 9.14, 5.70, and 7.78 mL/gVS, respectively, hindering hydrogen-producing bacteria dominance. However, higher FW concentrations facilitated rapid and strong substrate acidification at fermentation onset, effectively inhibiting the non-hydrogen producing bacteria and leading to a vast hydrogen production capacity of 68.63–120.78 mL/gVS. Rapid and substantial FW acidification is vital for effective inoculum treatment, highlighting its crucial role in this study. The findings support the potential use of FW inoculum treatment in generating highly productive microbial communities for hydrogen production. [Display omitted] • Acidification-based inoculum treatment of substrate enables cost-efficient H 2 production. • Variation in hydrogen production observed based on food waste concentrations. • Limited acidity inhibits H 2 production in low food waste concentration groups. • Rapid and strong acidification of substrate is crucial for successful inoculum pretreatment. • Inoculum treatment by food waste can generate productive microbial communities for H 2 production. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is an aggressive brain tumor with shorter median overall survival time. It is urgent to find novel methods to enhance the therapeutic efficiency clinically. miR-373 is related to the biological development process of cancers, but there are no reports whether modulation on miR-373 could affect GBM development or modify the efficiency of chemo- or radiotherapy yet. Our current study found that the higher level of miR-373 was observed in U-251 cells. Inhibition on miR-373 could reduce the U-251 cell number by 65% and PCNA expression obviously. In addition, inhibition on miR-373 sensitized U-251 cells to chemo- or radiotherapy. The cell cycle of U-251 cells could be modulated by miR-373 knockdown, which could enhance the p21 expression and reduce the cdc2 level. Anti-miR-373 could increase the Bax/Bcl-2 ratio of U-251 cells and induce cell apoptosis significantly. These above effects of miR-373 could be reversed by Limk1 overexpression. Thus, our experimental data confirmed the fact that miR-373 could be a new therapeutic target to enhance the efficiency of chemo- or radiotherapy for clinical GBM patients. [ABSTRACT FROM AUTHOR]

Background: The Charlson Comorbidity Index (CCI) can be automatically calculated from the International Classification of Disease (ICD) code. However, the feasibility of this transformation has not been acknowledged, particularly in hospitals without a qualified ICD coding system. Here, we investigated the utility of coding-based CCI in China.Methods: A multi-center, population-based, retrospective observational study was conducted, using a dataset incorporating 2,464,395 adult subjects from 15 hospitals. CCI was calculated using both ICD-10-based and diagnosis-based method, according to the transformation rule reported previously and to the literal description from discharge diagnosis, respectively. A κ coefficient of variation was used as a measure of agreement between the above two methods for each hospital. The discriminative abilities of the two methods were compared using the receiver-of-operating characteristic curve (ROC) for prediction of in-hospital mortality.Results: Total agreement between the ICD-based and diagnosis-based CCI for each index ranged from 86.1 to 100%, with κ coefficients from 0.210 [95% confidence interval (CI) 0.208-0.212] to 0.932 (95% CI 0.924-0.940). None of the 19 indices of CCI had a κ coefficient > 0.75 in all the hospitals included for study. The area under the curve of ROC for in-hospital mortality of all 15 hospitals was significantly lower for ICD-based than diagnosis-based CCI [0.735 (0.732, 0.739) vs 0.760 (0.757, 0.764)], indicative of more limited discriminative ability of the ICD-based calculation.Conclusions: CCI calculated using ICD-10 coding did not agree with diagnosis-based CCI. ICD-based CCI displayed diminished discrimination performance in terms of in-hospital mortality, indicating that this method is not promising for CCI scoring in China under the present circumstances. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to evaluate the efficacy of machine learning (ML) techniques in predicting survival for chordoma patients in comparison with the standard Cox proportional hazards (CoxPH) model. Methods: Using a Surveillance, Epidemiology, and End Results database of consecutive newly diagnosed chordoma cases between January 2000 and December 2018, we created and validated three ML survival models as well as a traditional CoxPH model in this population-based cohort study. Randomly, the dataset was divided into training and validation datasets. Tuning hyperparameters on the training dataset involved a 1000-iteration random search with fivefold cross-validation. Concordance index (C-index), Brier score, and integrated Brier score were used to evaluate the performance of the model. The receiver operating characteristic (ROC) curves, calibration curves, and area under the ROC curves (AUC) were used to assess the reliability of the models by predicting 5- and 10-year survival probabilities. Results: A total of 724 chordoma patients were divided into training (n = 508) and validation (n = 216) cohorts. Cox regression identified nine significant prognostic factors (p < 0.05). ML models showed superior performance over CoxPH model, with DeepSurv having the highest C-index (0.795) and the best discrimination for 5- and 10-year survival (AUC 0.84 and 0.88). Calibration curves revealed strong correlation between DeepSurv predictions and actual survival. Risk stratification by DeepSurv model effectively discriminated high- and low-risk groups (p < 0.01). The optimized DeepSurv model was implemented into a web application for clinical use that can be found at https://hust-chengp-ml-chordoma-app-19rjyr.streamlitapp.com/. Conclusion: ML algorithms based on time-to-event results are effective in chordoma prediction, with DeepSurv having the best discrimination performance and calibration. [ABSTRACT FROM AUTHOR]

Background: Ellis–van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases. Methods: A Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole‐exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied. Results: WES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.‐164_174del, which ultimately leads to a 337 bp deletion at the 3′ end of exon 1 and loss of the start codon. Conclusion: This is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increasing trend in conducting seamless phase 2/3 clinical trials for drug development in the pharmaceutical industry due to the visible advantages compared with traditional approaches for separate phase 2 and 3 development. Innovative study designs have been proposed for seamless phase 2/3 trials, which mainly focus on the traditional aspects of study design, such as how to control the Type I error rate, sample size re-estimation after the phase 2 portion, and how to make treatment selection at the end of the phase 2 portion. However, there are still some questions unresolved such as how to determine the go/no-go boundary and how to plan the phase 2 portion sample size. In this paper, we discuss how to determine the phase 2 portion and phase 3 portion sample sizes as well as the corresponding go/no-go criteria for a seamless phase 2/3 oncology trial based on Probability of Success. In addition, we further expand the methodology to include designs with an interim look within the phase 2 portion to speed up the go/no-go decision-making process. In case of overwhelming efficacy, this design would further shorten the overall trial duration. In case of inefficacy, this design can stop the trial earlier without exposing more patients to inefficacious treatment. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors for early neurological deterioration (END) in acute lacunar stroke patients and its influence on functional outcome. Methods: Consecutive acute lacunar stroke patients defined by magnetic resonance imaging (MRI) between January 2018 and June 2020 were included in the study. END was defined as any persisting increase in National Institutes of Health Stroke Scale (NIHSS) score of ⩾ 2 points post admission, and favorable outcome was defined as a modified Rankin Scale (mRS) of 0–2 at discharge. Univariable and multivariable logistic regression were performed to identify risk factors related to END, as well as the influence of END on functional outcome. Results: Among a total of 638 lacunar stroke patients (420 males (65.8%), median age 66 years (interquartile range (IQR): 56–74)), 108 (16.9%) developed END, and 94.4% (102/108) of the END occurred within 72 h post admission. Admission NIHSS score (adjusted odds ratio (aOR) 1.132, 95% confidence interval (CI) 1.046–1.225, p = 0.002), female (aOR 2.752, 95% CI 1.277–5.933, p = 0.010), admission systolic blood pressure (SBP) (160–179 mm Hg) (aOR 9.395, 95% CI 4.310–20.479, p < 0.001) and admission SBP (⩾180 mm Hg) (aOR 16.030, 95% CI 5.991–42.891, p < 0.001) were significantly associated with END. Delay time from onset to admission (aOR 0.995, 95% CI 0.990–1.000, p = 0.031), SBP dropping (⩾20 mm Hg) within 3 days or when END occurred (aOR 0.037, 95% CI 0.016–0.086, p < 0.001) and thalamic lacunar infarction (aOR 0.098, 95% CI 0.012–0.827, p = 0.033) were inversely associated with END. END (aOR 12.374, 95% CI 6.881–22.254, p < 0.001) and higher admission NIHSS score (aOR 1.488, 95% CI 1.359–1.629, p < 0.001) predicted unfavorable outcome at discharge. Conclusion: END in lacunar stroke patients is common and is associated with unfavorable outcome. Admission high SBP is a potentially modifiable risk factor for prevention of END, but this needs further investigation. [ABSTRACT FROM AUTHOR]

Bone mesenchymal stem cells (BMSCs) play an important role in maintaining the dynamic balance of bone metabolism. Recent studies have reported that a decrease in the osteogenic function of MSCs is strongly associated with osteoporosis. Melatonin is a neuroendocrine hormone produced in the pineal gland and is essential in the physiological regulation. This study is aimed at exploring the effect of melatonin on MSCs osteoblastic differentiation and elucidate the underlying mechanisms. We isolated BMSCs from rat bone marrow and demonstrated that melatonin improved osteogenic differentiation of BMSCs by the alizarin red staining and ALP staining. We then showed that melatonin enhanced osteogenic gene expression in BMSCs, including ALP, Col 1, OCN, OPN, and RUNX2. We further revealed that melatonin inhibited the inflammatory response of BMSCs by suppressing the NF-κB signaling pathways. In light of this, we found that the NF-κB pathway-specific activator TNF-α activated the NF-κB pathway, inhibited osteogenic differentiation, and induced inflammatory response in BMSCs. Melatonin was found to reverse the inhibitory effect of TNF-α on osteogenic differentiation and inflammation in BMSCs. Taken together, these findings indicated that melatonin may have therapeutic potential to be used for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer (DFU) is one of the most common complications of diabetes, bringing physical and mental challenges for patients due to the lack of efficient curative therapy. Despite considerable advances in pharmacological and surgical approaches, clinical trials for DFU patients remain disappointing due to the local overactive and excessive inflammation. Immunomodulatory hydrogels has significant advantages to overcome the clinical challenge of DFUs therapy. Here, recent fabrication and regenerative advances in the utilization of functional hydrogels for altering the immune microenvironment of DFUs are comprehensively reviewed. The pathological features and the healing processes of DFUs, followed by summarizing the physicochemical properties essential for the design of regenerative hydrogels for immunomodulation in DFUs, are briefly introduced. Then, the potential immuno‐therapeutic modalities of hydrogels and emerging trends used to treat DFUs via multitherapeutic approaches and enhanced efficacy and safety are discussed. Taken together, by linking the structural properties of hydrogels to their functions in DFU therapy with a particular focus on immunomodulatory stimuli, this review can promote further advances in designing advanced hydrogels for DFUs, resulting in improved diabetic wound repair through translation into clinical setting in the near future. [ABSTRACT FROM AUTHOR]

Reference 1 Chen X, Peng Y, Xue H, Liu G, Wang N, Shao Z. MiR-21 regulating PVT1/PTEN/IL-17 axis towards the treatment of infectious diabetic wound healing by modifed GO-derived biomaterial in mouse models. A-C Representative digital pictures were collected at Day 0, 3, 7, 10 and 14 in the wound healing process and its statistical data, minor ticks' interval: 1 mm. [Extracted from the article]

Background: Patients with Parkinson's disease (PD) present various responsiveness to levodopa, but the cause of such differences in levodopa responsiveness is unclear. Previous studies related the damage of brain white matter (WM) to levodopa responsiveness in PD patients, but no study investigated the relationship between the structural brain network change in PD patients and their levodopa responsiveness. Methods: PD patients were recruited and evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). Each patient received a diffusion tensor imaging (DTI) scan and an acute levodopa challenge test. The improvement rate of UPDRS‐III was calculated. PD patients were grouped into irresponsive group (improvement rate < 30%) and responsive group (improvement rate ≥ 30%). Tract‐based spatial statistics (TBSS), deterministic tracing (DT), region of interest (ROI) analysis, and automatic fiber identification (AFQ) analyses were performed. The structural brain network was also constructed and the topological parameters were calculated. Results: Fifty‐four PD patients were included. TBSS identified significant differences in fractional anisotropy (FA) values in the corpus callosum and other regions of the brain. DT and ROI analysis of the corpus callosum found a significant difference in FA between the two groups. Graph theory analysis showed statistical differences in global efficiency, local efficiency, and characteristic path length. Conclusion: PD patients with poor responsiveness to levodopa had WM damage in multiple brain areas, especially the corpus callosum, which might cause disruption of information integration of the structural brain network. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal bone loss, mainly caused by excessive bone resorption mediated by osteoclasts, has become a global public health burden. Metformin, a hypoglycemic drug, has been reported to have beneficial effects on maintaining bone health. However, the role and underlying mechanism of metformin in ovariectomized (OVX)-induced bone loss is still vague. Results: In this study, we demonstrated for the first time that metformin administration alleviated bone loss in postmenopausal women and ovariectomized mice, based on reduced bone resorption markers, increased bone mineral density (BMD) and improvement of bone microstructure. Then, osteoclast precursors administered metformin in vitro and in vivo were collected to examine the differentiation potential and autophagical level. The mechanism was investigated by infection with lentivirus-mediated BNIP3 or E2F1 overexpression. We observed a dramatical inhibition of autophagosome synthesis and osteoclast formation and activity. Treatment with RAPA, an autophagy activator, abrogated the metformin-mediated autophagy downregulation and inhibition of osteoclastogenesis. Additionally, overexpression of E2F1 demonstrated that reduction of OVX-upregulated autophagy mediated by metformin was E2F1 dependent. Mechanistically, metformin-mediated downregulation of E2F1 in ovariectomized mice could downregulate BECN1 and BNIP3 levels, which subsequently perturbed the binding of BECN1 to BCL2. Furthermore, the disconnect between BECN1 and BCL2 was shown by BNIP3 overexpression. Conclusion: In summary, we demonstrated the effect and underlying mechanism of metformin on OVX-induced bone loss, which could be, at least in part, ascribed to its role in downregulating autophagy during osteoclastogenesis via E2F1-dependent BECN1 and BCL2 downregulation, suggesting that metformin or E2F1 inhibitor is a potential agent against postmenopausal bone loss. DbafFdrzVodu3S-ctJyDCG Video abstract [ABSTRACT FROM AUTHOR]

The ubiquitination-proteasome system (UPS) is crucial in regulating a variety of cellular processes including proliferation, differentiation, and survival. Ubiquitin protein ligase E3 is the most critical molecule in the UPS system. Dysregulation of the UPS system is associated with many conditions. Over the past few decades, there have been an increasing number of studies focusing on the UPS system and how it affects bone metabolism. Multiple E3 ubiquitin ligases have been found to mediate osteogenesis or osteolysis through a variety of pathways. In this review, we describe the mechanisms of UPS, especially E3 ubiquitin ligases on bone metabolism. To date, many E3 ubiquitin ligases have been found to regulate osteogenesis or osteoclast differentiation. We review the classification of these E3 enzymes and the mechanisms that influence upstream and downstream molecules and transduction pathways. Finally, this paper reviews the discovery of the relevant UPS inhibitors, drug molecules, and noncoding RNAs so far and prospects the future research and treatment. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of programmed cell death and an important type of biological catabolism. Through the action of divalent iron or ester oxygenase, ferroptosis can induce lipid peroxidation and cell death, regulating a variety of physiological processes. The role of ferroptosis in the modulation of bone homeostasis is a significant topic of interest. Herein, we review and discuss recent studies exploring the mechanisms and functions of ferroptosis in different bone-related cells, including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. The association between ferroptosis and disorders of bone homeostasis is also explored in this review. Overall, we aim to provide a detailed overview of ferroptosis, summarizing recent understanding on its role in regulation of bone physiology and bone disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcer (DFU), persistent hyperglycemia and inflammation, together with impaired nutrient and oxygen deficiency, can present abnormal angiogenesis following tissue injury such that these tissues fail to heal properly. It is critical to design a new treatment method for DFU patients with a distinct biomechanism that is more effective than current treatment regimens. Method: Graphene oxide (GO) was combined with a biocompatible polymer as a kind of modified GO-based hydrogel. The characterization of our biomaterial was measured in vitro. The repair efficiency of the biomaterial was evaluated in the mouse full-skin defect models. The key axis related to diabetic wound (DW) was identified and investigated using bioinformatics analyses and practical experiments. Result: In the study, we found that our modified GO-based wound dressing material is a promising option for diabetic wound. Secondly, our biomaterial could enhance the secretion of small EVs (sEVs) with more miR-21 by adipose-derived mesenchymal stem cells (AD-MSCs). Thirdly, the PVT1/PTEN/IL-17 axis was found to be decreased to promote DFU wound healing by modifying miR-21 with the discovery of PVT1 as a critical LncRNA by bioinformatics analysis and tests. Conclusion: These findings could aid in the development of clinical care strategies for DFU wounds. [ABSTRACT FROM AUTHOR]

Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSs) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3′-untranslated region (3′UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding. In silico analysis indicated that rs11169571 (T > C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying –T allele, but not the –C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to TT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 of ATF1 gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH. [ABSTRACT FROM AUTHOR]

Analysis on the degradation or chemical change of log after G. lucidum cultivation using FTIR. [Display omitted] • Analysis on the degradation of cultivated log with G. lucidum using FTIR. • The composition of cultivated logs was explored and reported with numerous changes. • Deduction of cellulose and lignin peaks proven the decay of log influenced by the duration. • Year 4 log spectrum indicated the highest degradation under the process compare. • 2DIR has determined the sequence active autopeaks according the different assignment. The popular medicinal mushroom Ganoderma lucidum was often cultivated by the natural-log. Generally the short log after cultivation were discarded and became pollutant. Rapid and less destructive method of analysis technical by Fourier Transform Infrared (FTIR) and Two-dimension Infrared (2DIR) correlation spectroscopy were selected to determine the composition changes of the logs after G. lucidum cultivation after first year to fifth year. The FTIR accumulated spectra formed without processed baseline showed the samples relied upon a sequenced increase of higher level than spectrum control Q (Q = Quercus acuttisima) from L + Q-5 (L = Lingzhi), L + Q-3, L + Q-1 to L + Q-2. The spectrum L + Q-4 has the optimum highest peak at box B, C and E from this lumped spectral view. The split spectra pinpointed on the fingerprint region of a sample begins from peak 1737 cm−1. ascribed C = O stretching vibration on acetyl and carboxyl hemicellulose group bonding gradually faded from L + Q-1 to L + Q-4 but appeared again on L + Q-5, possibly due to the degradation of hemicellulose. The absorption of peak around 1626 cm−1,1318 cm−1 and 781 cm−1 could be the characteristic absorption peak of calcium oxalate monohydrate. The correlation table indicated, most of the original structure of the building block of the wooden part was deteriorated and marked the lowest correlation value of the 4th year sample with control Q. The sudden changing pattern of 2nd derivative spectrum L + Q-3 to more flatten pattern spectrum L + Q-4 ascribed the changing contents of cellulose and hemicellulose included the lignin within one year during the G. lucidum cultivation. The 2DIR spectrum of the raw material sample precisely showed that the active site with red color was clustered with the area around 1800–1700 cm−1, 1450–800 cm−1 and 750–400 cm−1. In between, the range 1450–800 cm−1 was the most active cluster. Each of the sample showed the different sequence of autopeak comparison. This study has examined the impact of G. lucidum on the degradation of Q. acuttisima in term of their ecosystem life chain. The components of healthy Q. acuttisima wood including lignin, cellulose, hemicellulose and calcium oxalate monohydrate underwent changes after different years of G. lucidum cultivation. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the intraoperative and early postoperative clinical outcomes of using an acromioclavicular joint hook plate (AJHP) versus a locking plate (LP) in the treatment of anterior sternoclavicular joint dislocation.Methods: Seventeen patients with anterior sternoclavicular joint dislocation were retrospectively analyzed from May 2014 to September 2019. Six patients were surgically treated with an AJHP, and 11 were surgically treated with an LP. Five male and one female patients composed the AJHP group, and nine male and two female patients composed the LP group. The mean age of all patients was 49.5 years.Results: Reduction and fixation were performed with AJHP or LP in all 17 patients. The mean operative blood loss, operative time, and length of incision in the AJHP group were significantly better than those in the LP group. Shoulder girdle movement of the AJHP group was significantly better than that of the LP group.Conclusions: This study revealed that AJHP facilitated glenohumeral joint motion, reduced the risk of rupture of mediastinal structures, required a shorter incision, and had lesser blood loss and a shorter duration of operation compared with LP. However, some deficiencies require further improvement. [ABSTRACT FROM AUTHOR]

Serum fetuin A has been shown to be associated with the risk of vascular calcification and atherosclerosis, and it can predict the onset of cardiovascular mortality in dialysis patients. The carotid intima-media thickness (cIMT) is an accessible and reliable method to identify the subclinical atherosclerosis. The aim of this study was to investigate the relationships between dialysate calcium concentrations and fetuin A or cIMT in patients undergoing peritoneal dialysis (PD). Forty patients, newly diagnosed end-stage renal disease (ESRD) and undergoing peritoneal dialysis, were enrolled in the study, with a calcium content of the peritoneal dialysis (PD) solution of 1.25 mmol/L in 20 patients (low-Ca group) and 1.75 mmol/L in 20 patients (standard-Ca group). The patients were followed up for 12 months after the PD conducted. Serum fetuin A was determined using a human fetuin A enzyme-linked immunosorbent assay kit and cIMT was detected using ultrasonic wave. We observed no difference between two groups with regard to the baseline data of fetuin A, cIMT, calcium, phosphorus, calcium-phosphorus product, high sensitivity CRP (hsCRP), parathyroid hormone (PTH), or lipid parameters. After 12 months follow-up, fetuin A (263.92 ± 16.1 vs. 282.76 ± 21.0, p = 0.017) and calcium-phosphorus product (39.85 ± 7.76 vs. 47.50 ± 6.65, p = 0.009) were obviously lower in the low-Ca group than standard-Ca group, the other serum parameters were not different between these two groups. Compared with baseline data, serum fetuin A concentration significantly reduced in low-Ca group ( p < 0.05). The number of patients with increased cIMT and newly occurring cardiovascular events in the low-Ca group were significantly reduced than standard-Ca group ( p < 0.05). In conclusion, our data suggest that low calcium dialysate treatment is associated with the decreased serum fetuin A concentration and serum calcium-phosphorus product, and it is associated with the reduced number of PD patients with increased cIMT or with newly occurring cardiovascular events. However, more studies with lager sample size should be performed in the future. [ABSTRACT FROM AUTHOR]

Contact lens sensors have been emerging as point-of-care devices in recent healthcare developments for ocular physiological condition monitoring and diagnosis. Fluorescence sensing technologies have been widely applied in contact lens sensors due to their accuracy, high sensitivity, and specificity. As ascorbic acid (AA) level in tears is closely related to ocular inflammation, a fluorescent contact lens sensor incorporating a BSA-Au nanocluster (NC) probe is developed for in situ tear AA detection. The NCs are firstly synthesized to obtain a fluorescent probe, which exhibits high reusability through the quench/recover (KMnO 4 /AA) process. The probe is then encapsulated with 15 wt% of poly(vinyl alcohol) (PVA) and 1.5 wt% of citric acid (CA) film, and implemented on a closed microfluidic contact lens sensing region. The laser-ablated microfluidic channel in contact lens sensors allows for tear fluid to flow through the sensing region, enabling an in-situ detection of AA. Meanwhile, a smartphone application accompanied by a customized 3D printed readout box is developed for image caption and algorism to quantitative analysis of AA levels. The contact lens sensor is tested within the readout box and the emission signal is collected through the smartphone camera at room temperature with an achieved LOD of 0.178 mmol L-1 (0.0–1.2 mmol L-1). The operational and storage lifetime is also evaluated to characterize the sensor properties and resulted in 20 h and 10 days, respectively. The reusable AA contact lens sensor is promising to lead to an alternative accessible diagnostic method for ocular inflammation in point-of-care settings. [ABSTRACT FROM AUTHOR]

Fracture healing is a complex biological process that involves the orchestrated interplay of various cells and molecular signaling pathways. Among the key players, macrophages have emerged as critical regulators of fracture repair, influencing inflammation, tissue remodeling, and angiogenesis. Recent advances in hydrogel-based therapeutics have provided exciting opportunities to leverage the modulatory effects of macrophages for improving fracture healing outcomes. In the present study, we review the importance of macrophages in fracture repair and their potential therapeutic role in hydrogel-based interventions. We discuss the molecular mechanisms underlying macrophage-mediated effects on fracture healing, and how hydrogels can be utilized as a platform for macrophage modulation. Furthermore, we highlight the translation of hydrogel-based therapies from bench to bedside, including preclinical and clinical studies, and the challenges and opportunities in harnessing the therapeutic potential of macrophages in fracture repair. Overall, understanding the importance of macrophages in fracture healing and the potential of hydrogel-based therapeutics to modulate macrophage responses can pave the way for developing innovative approaches to improve fracture healing outcomes. The review encompasses an intricate exploration of diverse macrophage phenotypes, strategies for fine-tuning hydrogel properties to regulate immune responses, wide-ranging applications across bone healing scenarios, and ongoing clinical trials highlighting translational progress. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the clinical application of double-reverse traction for minimally invasive reduction of complex tibial plateau fractures. A retrospective analysis was performed to identify all patients admitted to the Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from March 2017 to December 2019 with Schatzker type VI tibial plateau fractures. 12 patients were identified (7 men and 5 women) with an average age of 46.15 ± 13 (39-58) years old. All patients were treated with double-reverse traction and closed reduction. After the fracture was reduced, the bone plate was fixed by percutaneous minimally invasive implantation. Outcomes assessed in this study include operation time and intraoperative blood loss. Imaging was performed during the postoperative follow-up, and functional recovery was evaluated at the final follow-up according to the Hospital for Special Surgery (HSS) score and the International Knee Joint Literature Committee (IKDC) functional score. Patients were followed up for 12.54 ± 1.5 (8-15) months. The average operation time was 63.63 ± 21 (35-120) minutes, and the average intraoperative blood loss was 105.45 ± 21 (60-200) mL. The Rasmussen imaging score was either excellent or good in all cases. The knee joint HSS score was 86.15 ± 6 (79-90) points, and the IKDC score was 80.01 ± 11 (75-90) points. No complications, such as wound infection, incision disunion, loosening of internal fixation, and internal fixation failure, occurred. In the treatment of Schatzker VI type complex tibial plateau fracture, the dual-reverse traction minimally invasive technique has the advantages of safety and effectiveness, less soft tissue injury, and allowing early joint movement, which is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability. [ABSTRACT FROM AUTHOR]

Background: Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Results: We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. Conclusions: PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing. [ABSTRACT FROM AUTHOR]

Background: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined. Materials and methods: Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3. Results: A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42–4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55–1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found. Conclusions: The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments. [ABSTRACT FROM AUTHOR]

The placenta becomes one of the most diversified organs during placental mammal radiation. The main in vitro model for studying mouse trophoblast development is the 2D differentiation model of trophoblast stem cells, which is highly skewed to certain lineages and thus hampers systematic screens. Here, we established culture conditions for the establishment, maintenance, and differentiation of murine trophoblast organoids. Murine trophoblast organoids under the maintenance condition contain stem cell-like populations, whereas differentiated organoids possess various trophoblasts resembling placental ones in vivo. Ablation of Nubpl or Gcm1 in trophoblast organoids recapitulated their deficiency phenotypes in vivo , suggesting that those organoids are valid in vitro models for trophoblast development. Importantly, we performed an efficient CRISPR-Cas9 screening in mouse trophoblast organoids using a focused sgRNA (single guide RNA) library targeting G protein-coupled receptors. Together, our results establish an organoid model to investigate mouse trophoblast development and a practicable approach to performing forward screening in trophoblast lineages. [Display omitted] • Murine trophoblast organoids can be derived from placentae or trophoblast stem cells • Murine trophoblast organoids exhibit features of their placental trophoblast counterparts • Ablation of essential genes in trophoblast organoids recapitulates in vivo placental defects • Murine trophoblast organoids can be used for CRISPR-Cas9 screening Mao, Ye, Xu, Jiang et al. established murine trophoblast organoids, which can be used to model mouse placental development and perform high-throughput genetic screening in a dish. [ABSTRACT FROM AUTHOR]

[Display omitted] • SIF extraction reducing the interference from soil background and canopy structure improved the LCC estimation accuracy. • OSAVI segmentation could eliminate the soil background interference for SIF extraction. • Brightness extracted from hue-saturation-intensity color space was to quantify the canopy light distribution. • Shadowed region clustering based on brightness was optimal region for SIF extraction. • SIF modified by brightness outperformed due to relationship between brightness and canopy structure. Accurate estimation of leaf chlorophyll content (LCC) in field for wheat crops is important to provide guidance for precision management. Solar-induced chlorophyll fluorescence (SIF) extraction based on hyperspectral imaging is an effective tool for LCC estimation, which is because SIF is a signal directly and intrinsically related to photosynthetic activity of crops. However, soil background and structural difference always lead to mixing of soil, shadowed and sunlit canopy components, and heterogeneous light distribution among canopy, which increase the complexity of SIF extraction and reduce the LCC estimation accuracy. The purpose of this study is to propose an accurate SIF extraction method by eliminating above challenges to improve the LCC estimation accuracy. Hyperspectral image and LCC measurements were conducted at the jointing and heading stages of wheat crops. Firstly, to eliminate the effect of soil background, two image segmentation methods, excess green index (ExG) and optimized soil-adjusted vegetation index (OSAVI), are compared to extract the crop region. Secondly, to reduce the canopy structure effect, light distribution condition is evaluated by the brightness, which is extracted from intensity component of hue-saturation-intensity color space. Then K-means clustering based on the brightness distribution is utilized to divide the segmented crop region further into shadowed and sunlit regions. Finally, SIF was extracted based on the Fraunhofer line discriminator method at 687 and 761 nm, and was modified by normalization of brightness to reduce the influence of heterogeneous light distribution. The performance of random forest regression models, which are built by extracting SIF based on raw image, segmented crop by ExG segmentation, segmented crop by OSAVI segmentation, and shadowed and sunlit regions, respectively, is compared. Results show the estimation accuracy of the models increases when image segmentation is performed (determination coefficient of prediction set (R P 2) = 0.37 for ExG segmentation; R P 2 = 0.47 for OSAVI segmentation) compared with raw image (R P 2 = 0.30). Moreover, shadowed region clustering based on brightness was optimal region for SIF extraction (R P 2 = 0.54) compared with the sunlit region (R P 2 = 0.27). The modified SIF at shadowed regions, normalized by the brightness of crops to reduce the effect of heterogeneous light distribution, yields the highest relationship with LCC (R P 2 = 0.79), which outperforms SIF normalized by the absorbed photosynthetically active radiation (APAR). The reason is that brightness is more related to LAI, a parameter representing canopy structure, than APAR. It suggests that OSAVI segmentation for soil background effect elimination and SIF extraction considering canopy structure and heterogeneous light distribution facilitate the improvement of LCC estimation accuracy for high-throughput phenotyping in field. [ABSTRACT FROM AUTHOR]

Background and purpose — Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods — In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results — Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24–48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation — In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications. [ABSTRACT FROM AUTHOR]

CONTEXTE: Les atteintes cardiaques sont fréquentes dans les cas graves de maladie à coronavirus 2019 (COVID-19) et sont associées à un mauvais pronostic. Notre étude portait sur les facteurs prédictifs de mortalité intrahospitalière, les caractéristiques de l'arythmie et les effets des traitements qui allongent l'intervalle QT chez les patients ayant une atteinte cardiaque. MÉTHODES: Nous avons fait une étude de cohorte rétrospective des cas graves de COVID-19 admis à l'hôpital Tongji, à Wuhan, en Chine, entre le 29 janvier et le 8 mars 2020. En examinant ceux qui avaient une atteinte cardiaque, définie ici comme un taux élevé de troponine I cardiaque (TnIc), nous avons déterminé les caractéristiques biologiques et cliniques associées à la mortalité et au besoin de ventilation invasive. RÉSULTATS: Parmi les 1284 cas graves de COVID-19, 1159 avaient au dossier un taux de TnIc mesuré à l'admission, qui pour 170 (14,7 %) participants indiquait une atteinte cardiaque. Les patients ayant une atteinte cardiaque avaient un taux de mortalité nettement plus élevé que les autres patients (71,2 % c. 6,6 %; p < 0,001). Nous avons constaté que le taux de TnIc initial (pour chaque augmentation d'un facteur 10, rapport de risque [HR] 1,32, intervalle de confiance [IC] à 95 % 1,06–1,66) et le taux de TnIc maximal atteint au cours de la maladie (pour chaque augmentation d'un facteur 10, HR 1,70, IC à 95 % 1,38–2,10) étaient associés à de minces chances de survie. Le taux de TnIc maximal était aussi associé au besoin de ventilation invasive (rapport de cotes 3,02, IC à 95 % 1,92–4,98). Sur les 170 patients ayant une atteinte cardiaque, 44 (25,9 %) présentaient une arythmie. Les 6 qui souffraient de tachycardie ou de fibrillation ventriculaires sont morts. Nous avons remarqué que les patients qui recevaient des médicaments allongeant l'intervalle QT avaient un intervalle QTc plus long que ceux qui n'en recevaient pas (différence entre les médianes 45 ms; p = 0,01), mais que ce traitement n'était pas directement lié à la mortalité (HR 1,04, IC à 95 % 0,69–1,57). INTERPRÉTATION: Chez les patients ayant la COVID-19 et une atteinte cardiaque, les taux initial et maximal de TnIc sont associés à de minces chances de survie, et le taux maximal est un facteur prédictif du besoin de ventilation invasive. Les malades de la COVID-19 doivent subir un dépistage des atteintes cardiaques et être surveillés, surtout si on leur fait suivre un traitement qui peut prolonger la repolarisation. Enregistrement de l'essai : Registre des essais cliniques chinois, n° ChiCTR2000031301. [ABSTRACT FROM AUTHOR]

Conventional seamless phase 2/3 design with fixed sample size determination (SSD) has gained its popularity in oncology drug development due to attractive features such as significantly shortening the development timeline, minimizing sample size, as well as early decision making. However, this design is not immune to inaccurate treatment effect assumption when only limited efficacy data are available at study design stage. We propose an innovative seamless phase 2/3 study design with flexible SSD for oncology trials, in which the trial is designed under a distribution of treatment effect instead of one single assumption due to huge uncertainty of treatment effect at design stage and the sample size for end of phase 3 analysis is not predetermined at design stage, but rather dynamically determined based on observed treatment effect at phase 2 portion. Some practical sample size determination rules for end of phase 3 analysis will be discussed. The proposed design can lead to reduced sample size or/and improved power compared with conventional seamless phase 2/3 design with fixed SSD. This innovative study design can be especially useful for programs with aggressive development strategy to expedite the process in delivering efficacious treatment to patients. [ABSTRACT FROM AUTHOR]

Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic. [ABSTRACT FROM AUTHOR]