Facilely tuning the intrinsic catalytic sites of the spinel oxide for peroxymonosulfate activation: From fundamental investigation to pilot-scale demonstration.

Heterogeneous peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have shown a great potential for pollutant degradation, but their feasibility for large-scale water treatment application has not been demonstrated. Herein, we develop a facile coprecipitation method for the scalable production (∼10 kg) of the Cu-Fe-Mn spinel oxide (CuFeMnO). Such a catalyst has rich oxygen vacancies and symmetry-breaking sites, which endorse it with a superior PMS-catalytic capacity. We find that the working reactive species and their contributions are highly dependent on the properties of target organic pollutants. For the organics with electron-donating group (e.g., -OH), high-valent metal species are mainly responsible for the pollutant degradation, whereas for the organics with electron-withdrawing group (e.g., -COOH and -NO2), hydroxyl radical (•OH) as the secondary oxidant also plays an important role. We demonstrate that the CuFeMnO-PMS system is able to achieve efficient and stable removal of the pollutants in the secondary effluent from a municipal wastewater plant at both bench and pilot scales. Moreover, we explore the application prospect of this PMS-based AOP process for large-scale wastewater treatment. This work describes an opportunity to scalably prepare robust spinel oxide catalysts for water purification and is beneficial to the practical applications of the heterogeneous PMS-AOPs.

Clinical and Prognostic Characteristics of Acute BAD-Related Stroke: A Multicenter MRI-Based Prospective Study.

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Stable Inorganic Colloidal Tin and Tin-Lead Perovskite Nanocrystals with Ultralong Carrier Lifetime via Sn(IV) Control.

Inorganic tin (Sn) perovskite nanocrystals offer a promising solution to the potential toxicity concerns associated with their established lead (Pb)-based counterparts. Yet, achieving their superior stability and optoelectronic properties remains an ongoing challenge. Here, we report a synthesis of high-symmetry α-phase CsSnI3 nanocrystals with an ultralong 278 ns carrier lifetime, exceeding previous benchmarks by 2 orders of magnitude through meticulous Sn(IV) control. The nanocrystals demonstrate excellent colloidal stability, uniform monodispersity, and a distinct exciton peak. Central to these outcomes is our designed solid-liquid antioxidation suspension of tri-n-octylphosphine (TOP) and zerovalent tin (Sn(0)) that fully addresses the unique coexisting oxygen-driven and solvent-driven Sn oxidation mechanisms in Sn perovskite nanocrystal synthesis. We uncover the largely undervalued function of TOP in mitigating oxygen-driven Sn oxidation and introduce Sn(0) powder to generate a synergistic antioxidation function with TOP, significantly reducing Sn(IV)-induced defects and distortions and contributing to enhanced optoelectronic properties. Strikingly, this approach also profoundly impacts inorganic Sn-Pb perovskite nanocrystals, boosting lifetimes by 2 orders of magnitude and increasing photoluminescence quantum yield over 100-fold to 35%. Our findings illuminate the potential of Sn-based nanocrystals for optoelectronic applications.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

The significance of guiding anterior cruciate ligament revision: a modified femoral tunnel classification.

BACKGROUND: The positioning error of femoral tunnel was the key factor leading to the failure of anterior cruciate ligament (ACL) reconstruction. This study aimed to propose a new femoral tunnel classification to guide revision ACL reconstruction. METHODS: Totals of 150 patients with ACL reconstruction failure from 2017 to 2023 were enrolled in this retrospective study. According to the tunnel diameter, shape, posterior wall and the positioning relationship with the Lateral Intercondylar Ridge on the three-dimensional CT imaging, we divided the femoral tunnels into four types: Type I off-target type, Type II straddled type, Type III anatomical type, and Type IV irregular type. Finally, explored the inter-observer reliability within two groups of doctors (Group A, 12 high seniorities; Group B, 12 low seniorities), and evaluated the intra-observer reliability within 6 doctors after two months. Clinical evaluation was performed using the Lysholm score, Tenger activity score, Pivot Shift and anterior knee laxity measurements. RESULTS: Among 150 cases of femoral tunnel three-dimensional CT reconstructed imaging, 144 cases were successfully included in the classification system, and 6 cases were confirmed as uncertain type. We measured the Kappa (κ) coefficient of group A was significantly higher than that of group B (κ 0.72 VS 0.68), and the κ coefficient of group A was still higher than group B (κ 0.69 VS 0.62) after further dividing Type III anatomical type into three subtypes. In addition, the κ coefficients of intra-observer reliability were all exceeded 0.73. Clinical follow-up showed that 9 patients had good knee joint motor function and stability after operation. CONCLUSION: The new femoral tunnel classification was reliable and had clinical guiding significance based on three-dimensional CT imaging. LEVEL OF EVIDENCE: Level III.

Accuracy and Consistency of 3-Dimensional Magnetic Resonance Imaging Is Comparable With 3-Dimensional Computed Tomography in Assessing Glenohumeral Instability: A Systematic Review.

PURPOSE: To compare the accuracy of 3-dimensional (3D) magnetic resonance imaging (MRI) with that of 3D computed tomography (CT) in evaluating glenoid bone loss (GBL). METHODS: This review aligned with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were obtained from data inception to August 28, 2023. The search term "glenoid bone loss" was extracted and analyzed via stringent inclusion and exclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 combined with the QUADAS-Comparative to assess the heterogeneity of included studies. RESULTS: A total of 1,589 related studies were retrieved, and 10 studies were finally included, of which a total of 143 shoulders were evaluated. The index test in QUADAS-Comparative was low risk in 9 studies. 3D MRI measurements of GBL were primarily best-fit circles (n = 9). In both clinical and cadaveric studies, the mean percentages of GBL measured by 3D MRI were 0.38% to 2.19% and 0.25% to 6.1% when compared with 3D CT and standard reference values, respectively. Intraclass correlation coefficient agreement greater than 0.9 between GBL percentages measured by 3D CT and 3D MRI. 3D MRI also could accurately measure glenoid width, glenoid height, humeral head width, and height. 3D MRI reconstruction time was similar to that of 3D CT, which was mainly 10 to 15 minutes. CONCLUSIONS: In both clinical and cadaveric studies, compared with 3D CT, 3D MRI is accurate and consistent in assessing glenohumeral bone, especially in measuring GBL, and the reconstruction time of 3D MRI is similar to 3D CT. LEVEL OF EVIDENCE: Level Ⅲ, systematic review of Level Ⅱ-Ⅲ studies.

Outcomes from different aspects indicate the all-inside technique may serve as an ideal option for anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the postoperative outcomes of the all-inside technique in arthroscopic anterior cruciate ligament reconstruction (ACLR). METHODS: Patients who underwent ACLR using the all-inside technique between 2018 and 2021 were retrospectively assessed. All patients were followed up for at least 2 years. Functional recovery and pain relief were assessed using the International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). Instrumented laxity was assessed via side-to-side difference using the Kneelax3 arthrometer. Graft maturity was estimated using the signal-to-noise quotient value based on magnetic resonance imaging (MRI). Adverse events during and after the surgery were recorded. RESULTS: A total of 78 patients were included in this study, with a mean age of 28.1 ± 7.6 years. The IKDC (p < 0.001), Lysholm (p < 0.001) and KOOS (p < 0.001 for all subgroups) scores at the final follow-up were significantly higher than those before the surgery. The VAS scores (p < 0.05) were significantly lower than those before surgery. The side-to-side difference results indicated that 50 patients had a difference of less than 3 mm, indicating a tight graft, whereas only 1 patient had a difference of >5 mm, indicating a loose graft. The median signal-to-noise quotient of the graft on MRI was 1.4 (P25, P75: 1.0, 2.0). No intraoperative adverse events were observed. Postoperative adverse events included three cases of infection, three cases of graft rerupture, two cases of cyclops lesion and one case of surgical intervention for a meniscal tear. CONCLUSION: ACLR using the all-inside technique offers promising results in patients with ACL rupture. LEVEL OF EVIDENCE: Level IV.

Gradual stabilization and narrowing of bone tunnels following primary anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study is to dynamically assess variations in tunnel diameters following anterior cruciate ligament reconstruction (ACLR) and investigate correlations with patient-reported outcomes (PROs) and graft maturity based on signal-to-noise quotient (SNQ). METHODS: Tunnel diameter and tunnel position were measured using three-dimensional models derived from computed tomography (CT) data. Postoperative graft maturity and integration were evaluated using magnetic resonance imaging (MRI). Clinical outcomes were assessed through PROs, which included the International Knee Documentation Committee Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Scores and Lysholm scores. The correlation between tunnel enlargement extent, PROs and SNQ values, as well as correlations between confounding factors, tunnel diameter differences and SNQ were analyzed. RESULTS: A total of 73 participants underwent primary ACLR and scheduled follow-ups. At the segment of the articular aperture, the femoral tunnel was enlarged by 32.3% to 10.4 ± 1.6 mm (p < 0.05), and the tibial tunnel was widened by 17.2% to 9.6 ± 1.2 mm (p < 0.05) at the 6-month follow-up. At 1 year postoperatively, diameters at the articular aperture were not further increased on the femoral (n.s.) and tibial (n.s.) sides. In early postoperative follow-up, the femoral tunnel was anteriorly and distally shifted, coupled with posterior and lateral deviation involving the tibial side, exhibiting minimal migration at 1-year follow-up. The degree of tunnel widening was not correlated with PROs and SNQ values. Age, gender, body mass index (BMI), time from surgery to follow-up, concomitant injuries and autograft type were not correlated with tunnel diameter differences and SNQ. CONCLUSIONS: The femoral and tibial bone tunnels exhibited eccentrical widening and gradually stabilized at 1 year following ACLR. Furthermore, the enlarged bone tunnels were not correlated with unsatisfied PROs and inferior graft maturity. LEVEL OF EVIDENCE: Level IV.

Safety of Early Surgery in Hip Fracture Patients Taking Clopidogrel and/or Aspirin: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to investigate the safety of early surgery in hip fracture patients who took clopidogrel and/or aspirin. METHODS: A systematic search was conducted using databases, including PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science, for studies relating to early arthroplasty or internal fixation for femoral neck fractures, intertrochanteric fractures, and subtrochanteric fractures in patients taking clopidogrel and/or aspirin. A total of 20 observational studies involving 3,077 patients were included in this meta-analysis, and analyzed in groups of early surgery versus delayed surgery, and clopidogrel and/or aspirin versus nonantiplatelet agents. RESULTS: Patients in the clopidogrel and/or aspirin group who underwent early surgery had significantly more intraoperative blood loss than those in the non-antiplatelet group (mean difference = 17.96, 95% confidence interval [CI] [4.37, 31.55], P = .01), and patients in the clopidogrel and/or aspirin group had a lower overall incidence of complications after early surgery than those in the delayed surgery group (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001) and a shorter length of hospital stay (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001). There was no significant difference in postoperative mortality and other related indicators. CONCLUSIONS: Early surgery in hip fracture patients taking clopidogrel and/or aspirin appears to be safe based on the available evidence and needs to be clarified by higher quality studies. However, the increased risk of cardiovascular events associated with discontinuation of clopidogrel or clopidogrel combined with aspirin dual antiplatelet therapy requires attention in the perioperative period.

Biochar and nano biochar: Enhancing salt resilience in plants and soil while mitigating greenhouse gas emissions: A comprehensive review.

Salinity stress poses a significant challenge to agriculture, impacting soil health, plant growth and contributing to greenhouse gas (GHG) emissions. In response to these intertwined challenges, the use of biochar and its nanoscale counterpart, nano-biochar, has gained increasing attention. This comprehensive review explores the heterogeneous role of biochar and nano-biochar in enhancing salt resilience in plants and soil while concurrently mitigating GHG emissions. The review discusses the effects of these amendments on soil physicochemical properties, improved water and nutrient uptake, reduced oxidative damage, enhanced growth and the alternation of soil microbial communities, enhance soil fertility and resilience. Furthermore, it examines their impact on plant growth, ion homeostasis, osmotic adjustment and plant stress tolerance, promoting plant development under salinity stress conditions. Emphasis is placed on the potential of biochar and nano-biochar to influence soil microbial activities, leading to altered emissions of GHG emissions, particularly nitrous oxide(N2O) and methane(CH4), contributing to climate change mitigation. The comprehensive synthesis of current research findings in this review provides insights into the multifunctional applications of biochar and nano-biochar, highlighting their potential to address salinity stress in agriculture and their role in sustainable soil and environmental management. Moreover, it identifies areas for further investigation, aiming to enhance our understanding of the intricate interplay between biochar, nano-biochar, soil, plants, and greenhouse gas emissions.

Differences in the effectiveness of leukocyte-rich platelet-rich plasma compared with leukocyte-poor platelet-rich plasma in the treatment of rotator cuff surgery: an umbrella review of meta-analyses.

BACKGROUND: An umbrella review of meta-analyses was conducted to evaluate the use of platelet-rich plasma (PRP) in arthroscopic surgeries of rotator cuff injury. The effectiveness of leukocyte-poor PRP and leukocyte-rich PRP in the treatment of rotator cuff surgery was also compared. METHODS: Web of Science, Embase, PubMed/MEDLINE, and the Cochrane Library were searched from inception to May 2024. Literature screening, quality evaluation, and data extraction were performed according to the inclusion and exclusion criteria. The Jadad decision algorithm was used to ascertain which meta-analysis represented the best evidence. RESULTS: A total of 11 meta-analyses with evidence level ranging from level 1 to 2 were included in this umbrella review. Leukocyte-poor PRP was effective in reducing rotator cuff retear rates, alleviating pain, and increasing Constant scores compared with non-PRP treatments. However, it did not show improvement on the University of California Los Angeles (UCLA) score, the American Shoulder and Elbow Surgeons (ASES) score, and the Simple Shoulder Test (SST) compared with the non-PRP treatment group. Meanwhile, the leukocyte-rich PRP group improved the SST but showed no different results when compared with the non-PRP treatment group. CONCLUSION: Compared with no use of PRP, leukocyte-poor PRP was able to alleviate postoperative pain, reduce the retear rate, and improve the postoperative Constant score. Leukocyte-rich PRP could effectively enhance postoperative SST outcomes, leading to improvement of patient satisfaction and quality of life. Future researches should prioritize long-term follow-up studies and evaluate the durability of these results.

Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders.

Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.

Clearance dysfunction of trans-barrier transport and lymphatic drainage in cerebral small vessel disease: Review and prospect.

Cerebral small vessel disease (CSVD) causes 20%-25% of stroke and contributes to 45% of dementia cases worldwide. However, since its early symptoms are inconclusive in addition to the complexity of the pathological basis, there is a rather limited effective therapies and interventions. Recently, accumulating evidence suggested that various brain-waste-clearance dysfunctions are closely related to the pathogenesis and prognosis of CSVD, and after a comprehensive and systematic review we classified them into two broad categories: trans-barrier transport and lymphatic drainage. The former includes blood brain barrier and blood-cerebrospinal fluid barrier, and the latter, glymphatic-meningeal lymphatic system and intramural periarterial drainage pathway. We summarized the concepts and potential mechanisms of these clearance systems, proposing a relatively complete framework for elucidating their interactions with CSVD. In addition, we also discussed recent advances in therapeutic strategies targeting clearance dysfunction, which may be an important area for future CSVD research.

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury.

BACKGROUND: Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. METHODS: TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. RESULTS: We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. CONCLUSION: In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.

New-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis.

The association between SARS-CoV-2 infection with increased risk for new-onset neurodegenerative diseases remains unclear. Therefore, this meta-analysis aims to elucidate whether new-onset neurodegenerative diseases are long-term sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched for articles published up to January 10, 2023. A systematic review and meta-analysis were performed to calculate the pooled effect size, expressed as hazard ratios (HR) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 33 146 809 individuals (2 688 417 post-COVID-19 cases and 30 458 392 controls) were included in the present meta-analysis. The pooled analyses compared with control groups showed a significant association between SARS-CoV-2 infection and increased risk for new-onset Alzheimer's disease (HR = 1.50, 95% CI 1.22-1.85, I2 = 97%), dementia (HR = 1.66, 95% CI 1.42-1.94, I2 = 91%), and Parkinson's disease (HR = 1.44, 95% CI 1.06-1.95, I2 = 86%) among COVID-19 survivors. SARS-CoV-2 infection may be associated with a higher risk for new-onset neurodegenerative diseases in recovered COVID-19 patients. Future studies are warranted to determine the biological mechanisms underlying the neurodegenerative consequences of COVID-19 as long-term sequelae of SARS-CoV-2 infection.

New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.

Bone marrow stromal cell-derived exosomal circular RNA improves diabetic foot ulcer wound healing by activating the nuclear factor erythroid 2-related factor 2 pathway and inhibiting ferroptosis.

BACKGROUND: Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA-itchy E3 ubiquitin protein ligase (circ-ITCH) was observed to be down-regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ-ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ-ITCH in wound healing of DFU remain undetermined. METHODS: Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8 (CCK-8) and tube formation assays, respectively. The interplays of circ-ITCH, TATA-Box-binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull-down assays. qRT-PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ-ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis-related makers. The mice DFU model was established to verify the in vitro results. RESULTS: Circ-ITCH was down-regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)-treated HUVECs. Overexpression of circ-ITCH or co-cultured with exosomal circ-ITCH from BMSCs could alleviate HG-induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ-ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ-ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time-dependent manner. CONCLUSION: Exosomal circ-ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.

Rapid-release reversible bonding of PMMA-based microfluidic devices with PBMA coating.

PMMA-based microfluidics have been widely used in various applications in biological and chemical fields. In the fabrication process of PMMA-based microfluidics, the substrate and cover plate usually need to be bonded to enclose the microchannel. The bonding process could be permanent or reversible. In some application scenarios, reversible bonding is needed to retrieve the samples inside the channel or reuse the chip. Current reversible bonding methods for PMMA-based microfluidics usually have drawbacks on bonding strength and contaminations from the adhesives used in the bonding process. In this study, a new approach is proposed for the reversible bonding of PMMA-based microfluidics, a layer of PBMA (with a very similar structure to PMMA) was coated on the surface of PMMA and then use the thermal fusion method to achieve the bonding with a high bonding strength, a tensile bonding strength of around 0.8 MPa was achieved. For debond process, a rapid temperature drop will trigger the immediate release of the bonding within several seconds. Detailed bonding strength measurement and biocompatibility tests were also conducted in this study. The proposed bonding method could have wide application potential in the fabrication of PMMA-based microfluidics.

Quorum sensing unveils the sludge floccule-assisted stabilization of aerobic granules in granule-dominated sequencing batch reactors.

Floccules are another major form of microbial aggregates in aerobic granular sludge systems. Previous studies mainly attributed the persistence of floccules to their relatively faster nutrient uptake and higher growth rate over aerobic granules; however, they failed to unravel the underlying mechanism of the long-term coexistence of these two aggregates. In this work, the existence and function of the floccules in an aerobic granule-dominated sequencing batch reactor were investigated from the view of quorum sensing (QS) and quorum quenching (QQ). The results showed that though the floccules were closely associated with the granules in terms of similar community structures (including the QS- and QQ-related ones), they exhibited a relatively higher QQ-related activity but a lower QS-related activity. A compatible proportion of floccules might be helpful to maintain the QS-related activity and keep the granules stable. In addition, the structure difference was demonstrated to diversify the QS- and QQ-related activities of the floccules and the aerobic granules. These findings could broaden our understanding of the interactions between the coexistent floccules and granules in aerobic granule-dominated systems and would be instructive for the development of the aerobic granular sludge process.

Shear-activated chemisorption and association of cyclic organic molecules.

Mechanochemical activation has created new opportunities for applications such as solvent-free chemical synthesis, polymer processing, and lubrication. However, mechanistic understanding of these processes is still limited because the mechanochemical response of a system is a complex function of many variables, including the direction of applied stress and the chemical features of the reactants in non-equilibrium conditions. Here, we studied shear-activated reactions of simple cyclic organic molecules to isolate the effect of chemical structure on reaction yield and pathway. Reactive molecular dynamics simulations were used to model methylcyclopentane, cyclohexane, and cyclohexene subject to pressure and shear stress between silica surfaces. Cyclohexene was found to be more susceptible to mechanochemical activation of oxidative chemisorption and subsequent oligomerization reactions than either methylcyclopentane or cyclohexane. The oligomerization trend was consistent with shear-driven polymerization yield measured in ball-on-flat sliding experiments. Analysis of the simulations showed the distribution of carbon atom sites at which oxidative chemisorption occurred and identified the double bond in cyclohexene as being the origin of its shear susceptibility. Lastly, the most common reaction pathways for association were identified, providing insight into how the chemical structures of the precursor molecules determined their response to mechanochemical activation.