Out with the old, in with the new: Meiotic driving of sex chromosome evolution.

Chromosomal regions with meiotic drivers exhibit biased transmission (> 50 %) over their competing homologous chromosomal region. These regions often have two prominent genetic features: suppressed meiotic crossing over and rapidly evolving multicopy gene families. Heteromorphic sex chromosomes (e.g., XY) often share these two genetic features with chromosomal regions exhibiting meiotic drive. Here, we discuss parallels between meiotic drive and sex chromosome evolution, how the divergence of heteromorphic sex chromosomes can be influenced by meiotic drive, experimental approaches to study meiotic drive on sex chromosomes, and meiotic drive in traditional and non-traditional model organisms with high-quality genome assemblies. The newly available diversity of high-quality sex chromosome sequences allows us to revisit conventional models of sex chromosome evolution through the lens of meiotic drive.

Achieving a Rapid Na+ Migration and Highly Reversible Phase Transition of NASICON for Sodium-Ion Batteries with Suppressed Voltage Hysteresis and Ultralong Lifespan.

Sodium ion batteries have attracted great attention for large scale energy storage devices to replace lithium-ion batteries. As a promising polyanionic cathode material of sodium-ion batteries, Na3V2(PO4)2F3 (NVPF) belonging to NASICON exhibits large gap space and excellent structural stability, leading to a high energy density and ultralong cycle lifespan. To improve its stability and Na ion mobility, K+ cations are introduced into NVPF crystal as in situ partial substitution for Na+. The influence of K+ in situ substitution on crystal structure, electronic properties, kinetic properties, and electrochemical performance of NVPF are investigated. Through ex situ examination, it turns out that K+ occupied Na1 ion, in which the K+ does not participate in the charge-discharge process and plays a pillar role in improving the mobility of Na+. Moreover, the doping of K+ cation can reduce the bandgap energy and improve the electronic conductivity. Besides, the optimal K+ doping concentration in N0.92K0.08VPF/C is found so as to achieve rapid Na+ migration and reversible phase transition. The specific capacity of N0.92K0.08VPF/C is as high as 128.8 mAh g-1 at 0.2 C, and at 10 C its rate performance is excellent, which shows a capacity of 113.3 mAh g-1.

A dwarf conifer tree from the Triassic of Antarctica: the first fossil evidence of suppressed growth in a favorable climate?

BACKGROUND AND AIMS: The complexity of fossil forest ecosystems is difficult to reconstruct due to the fragmentary nature of the fossil record. However, detailed morpho-anatomical studies of well-preserved individual fossils can provide key information on tree growth and ecology, including in biomes with no modern analog such as the lush forests that developed in the polar regions during past greenhouse climatic episodes. METHODS: We describe an unusual-looking stem from Middle Triassic (ca 240 Ma) deposits of Antarctica with over 100 very narrow growth-rings and conspicuous persistent vascular traces through the wood. Sections of the specimen were prepared using the cellulose acetate peel technique to determine its systematic affinities and analyse its growth. KEY RESULTS: The new fossil shows similarities with the form genus Woodworthia and with conifer stems from the Triassic of Antarctica, and is assigned to the conifers. Vascular traces are interpreted as those of small branches retained on the trunk. Growth-ring analyses reveal one of the slowest growth rates reported in the fossil record, with an average of 0.2 mm/season. While the tree was growing within the Triassic polar circle, sedimentological data and growth-ring information from other fossil trees, including from the same locality, support the presence of favorable conditions in the region. CONCLUSIONS: The specimen is interpreted as a dwarf conifer tree that grew under a generally favorable regional climate but whose growth was suppressed due to stressful local site conditions. This is the first time that a tree with suppressed growth is identified as such in the fossil record, providing new insights on the structure of polar forests under greenhouse climates and, more generally, on the complexity of tree communities in deep time.

A case of human diarrhea caused by Gallibacterium anatis: a case report.

Gallibacterium anatis (G. anatis) is an opportunistic pathogen previously associated with deaths in poultry and is also a pathogen that rarely causes human diseases. G. anatis has only been reported twice as the causative agent of a human disease (both in France). Here, we report a 62-year-old male patient with hypertension and type 2 diabetes who suffered from acute watery diarrhea caused by this bacterium which was identified by MALDI-TOF MS and 16 S rRNA sequencing. Despite human diarrhea caused by G.anatis is rare, with the continuous emergence of multidrug-resistant isolates of G. anatis in recent years, this case report will inform clinicians that G. anatis especially drug-resistant G. anatis may be a possible infectious source of human diarrhea in immune-suppressed populations.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Viral infection dynamics with immune chemokines and CTL mobility modulated by the infected cell density.

We study a viral infection model incorporating both cell-to-cell infection and immune chemokines. Based on experimental results in the literature, we make a standing assumption that the cytotoxic T lymphocytes (CTL) will move toward the location with more infected cells, while the diffusion rate of CTL is a decreasing function of the density of infected cells. We first establish the global existence and ultimate boundedness of the solution via a priori energy estimates. We then define the basic reproduction number of viral infection R 0 and prove (by the uniform persistence theory, Lyapunov function technique and LaSalle invariance principle) that the infection-free steady state E 0 is globally asymptotically stable if R 0 < 1 . When R 0 > 1 , then E 0 becomes unstable, and another basic reproduction number of CTL response R 1 becomes the dynamic threshold in the sense that if R 1 < 1 , then the CTL-inactivated steady state E 1 is globally asymptotically stable; and if R 1 > 1 , then the immune response is uniform persistent and, under an additional technical condition the CTL-activated steady state E 2 is globally asymptotically stable. To establish the global stability results, we need to prove point dissipativity, obtain uniform persistence, construct suitable Lyapunov functions, and apply the LaSalle invariance principle.

Value of radiomics-based automatic grading of muscle edema in polymyositis/dermatomyositis based on MRI fat-suppressed T2-weighted images.

BACKGROUND: The precise and objective assessment of thigh muscle edema is pivotal in diagnosing and monitoring the treatment of dermatomyositis (DM) and polymyositis (PM). PURPOSE: Radiomic features are extracted from fat-suppressed (FS) T2-weighted (T2W) magnetic resonance imaging (MRI) of thigh muscles to enable automatic grading of muscle edema in cases of polymyositis and dermatomyositis. MATERIAL AND METHODS: A total of 241 MR images were analyzed and classified into five levels using the Stramare criteria. The correlation between muscle edema grading and T2-mapping values was assessed using Spearman's correlation. The dataset was divided into a 7:3 ratio of training (168 samples) and testing (73 samples). Thigh muscle boundaries in FS T2W images were manually delineated with 3D-Slicer. Radiomics features were extracted using Python 3.7, applying Z-score normalization, Pearson correlation analysis, and recursive feature elimination for reduction. A Naive Bayes classifier was trained, and diagnostic performance was evaluated using receiver operating characteristic (ROC) curves and comparing sensitivity and specificity with senior doctors. RESULTS: A total of 1198 radiomics parameters were extracted and reduced to 18 features for Naive Bayes modeling. In the testing set, the model achieved an area under the ROC curve of 0.97, sensitivity of 0.85, specificity of 0.98, and accuracy of 0.91. The Naive Bayes classifier demonstrated grading performance comparable to senior doctors. A significant correlation (r = 0.82, P <0.05) was observed between Stramare edema grading and T2-mapping values. CONCLUSION: The Naive Bayes model, utilizing radiomics features extracted from thigh FS T2W images, accurately assesses the severity of muscle edema in cases of PM/DM.

A controlled study of MR DWI, FS-PDW, and CE-T1W imaging for the evaluation of the internal opening of anal fistulas.

BACKGROUND: Anal fistula (AF) is an abnormal tunnel under the skin connecting the anal canal in the colon to the skin of buttocks. Fat-suppressed (FS) proton density-weighted (PDW) imaging is mainly used for the diagnosis of diseases involving bones and joints. Until now, its value in the diagnosis of anal fistula has been rarely reported. PURPOSE: To compare three magnetic resonance imaging (MRI) sequences - diffusion-weighted imaging (DWI), FS-PDW), and contrast-enhanced (CE) T1-weighted (T1W) imaging - for the diagnostic value of the internal opening of AF. MATERIAL AND METHODS: MRI scans of 132 patients suspected of having AF between December 2021 and April 2023 were retrospectively analyzed. In total, 65 patients who underwent preoperative MRI and were treated surgically were included. The lesion conspicuity and accuracy for featuring AF were calculated by evaluating the three imaging datasets DWI, FS-PDW, and CE-T1W imaging, with surgical findings serving as the reference standard for the presence of fistulas. The statistical analysis included the application of the chi-square test and Kruskal-Wallis test. RESULTS: In 65 patients with AF, 87 internal openings of AF were confirmed. In terms of the diagnostic accuracy of the internal openings, both FS-PDW and CE-T1W imaging sequences were significantly better than DWI sequences, and the difference was statistically significant (P < 0.05). CONCLUSION: The FS-PDW imaging sequence showed comparable diagnostic performance of the internal opening of AF to CE-T1W imaging, which can provide an important diagnostic basis for clinical procedures.

[CT-Like MRI and Calcium-Suppressed Spectral CT Imaging of Multifocal Bone Infarcts in Both Lower Extremities:Report of One Case].

Bone infarction has a low incidence in clinical practice and mostly occurs in the metaphysis and diaphysis.Few studies report the advanced imaging technique for bone infarction.Here we reported the fast field echo resembling a CT using restricted echo-spacing and calcium-suppressed spectral CT imaging for a case of multifocal bone infarcts in both lower extremities,aiming to provide diagnostic experience for clinical practice.

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV) infection remains incurable due to the persistence of a viral reservoir despite antiretroviral therapy (ART). Cannabis (CB) use is prevalent amongst people with HIV (PWH), but the impact of CB on the latent HIV reservoir has not been investigated. METHODS: Peripheral blood cells from a cohort of PWH who use CB and a matched cohort of PWH who do not use CB on ART were evaluated for expression of maturation/activation markers, HIV-specific T-cell responses, and intact proviral DNA. RESULTS: CB use was associated with increased abundance of naive T cells, reduced effector T cells, and reduced expression of activation markers. CB use was also associated with reduced levels of exhausted and senescent T cells compared to nonusing controls. HIV-specific T-cell responses were unaffected by CB use. CB use was not associated with intact or total HIV DNA frequency in CD4 T cells. CONCLUSIONS: This analysis is consistent with the hypothesis that CB use reduces activation, exhaustion, and senescence in the T cells of PWH, and does not impair HIV-specific CD8 T-cell responses. Longitudinal and interventional studies with evaluation of CB exposure are needed to fully evaluate the impact of CB use on the HIV reservoir.

Highly Efficient Near-Infrared Luminescent Radicals with Emission Peaks over 750†nm.

Purely organic molecules exhibiting near-infrared (NIR) emission possess considerable potential for applications in both biological and optoelectronic technological domains, owing to their inherent advantages such as cost-effectiveness, biocompatibility, and facile chemical modifiability. However, the repertoire of such molecules with emission peaks exceeding 750 nm and concurrently demonstrating high photoluminescence quantum efficiency (PLQE) remains relatively scarce due to the energy gap law. Herein, we report two open-shell NIR radical emitters, denoted as DMNA-Cz-BTM and DMNA-PyID-BTM, achieved through the strategic integration of a donor group (DMNA) onto the Cz-BTM and PyID-BTM frameworks, respectively. We found that the donor-acceptor molecular structure allows the two designed radical emitters to exhibit a charge-transfer excited state and spatially separated electron and hole levels with non-bonding characteristics. Thus, the high-frequency vibrations are effectively suppressed. Besides, the reduction of low-frequency vibrations is observed. Collectively, the non-radiative decay channel is significantly suppressed, leading to exceptional NIR PLQE values. Specifically, DMNA-Cz-BTM manifests an emission peak at 758 nm alongside a PLQE of 55 %, whereas DMNA-PyID-BTM exhibits an emission peak at 778 nm with a PLQE of 66 %. Notably, these represent the pinnacle of PLQE among metal-free organic NIR emitters with emission peaks surpassing 750 nm.

Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression.

BACKGROUND & AIMS: Selgantolimod (GS-9688) is a Toll-like receptor 8 (TLR8) agonist that suppresses HBV in vitro. In a phase II study, we evaluated the safety and efficacy of weekly selgantolimod treatment in virally suppressed individuals with chronic HBV taking oral antiviral treatment. METHODS: Forty-eight patients were randomized into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative [n = 24 each]) to receive oral selgantolimod 3 mg, 1.5 mg, or placebo (2:2:1) once weekly for 24 weeks while maintaining oral antivirals. The primary efficacy endpoint was the percentage of patients with a ≥1 log10 IU/ml decline in hepatitis B surface antigen (HBsAg) from baseline to week 24. Post-treatment, patients continued on oral antivirals for 24 weeks. RESULTS: The primary endpoint was reached by one participant, who was HBeAg-negative and received selgantolimod 1.5 mg. In contrast with placebo-treated patients (n = 9), only selgantolimod-treated patients (n = 39 total) had HBsAg declines greater than 0.1 log10 IU/ml at weeks 24 (18%, 7/39) and 48 (26%, 10/39), HBsAg loss (5%, 2/39 through 48 weeks), or HBeAg loss (16%, 3/19 through 48 weeks). The most common adverse events in selgantolimod-treated groups were nausea (46%), upper respiratory tract infection (23%), and vomiting (23%). Gastrointestinal disorders were mostly mild and transient. Selgantolimod induced transient dose-dependent increases in serum cytokines, including IL-12p40, IFN-γ, and IL-1RA, as well as rapid redistribution of some circulating immune cell subsets. CONCLUSION: Oral selgantolimod up to 3 mg once weekly for 24 weeks was generally safe and well tolerated and led to serologic changes associated with progression to durable cure in two individuals by week 48. GOV IDENTIFIER: NCT03491553. IMPACT AND IMPLICATIONS: The only robust criterion for stopping treatment in chronic hepatitis B is loss of hepatitis B surface antigen (known as functional cure), which is rare during nucleos(t)ide analogue therapy. It is likely that novel antiviral and immunomodulatory therapies will be needed to achieve finite functional cure. Selgantolimod is an oral Toll-like receptor 8 agonist that has shown antiviral activity in vitro as well as safety in a phase I clinical trial with weekly dosing. In this phase II study, selgantolimod therapy was associated with transient increases in serum cytokines, rapid redistribution of circulating immune cell subsets, modest reductions in HBsAg and HBeAg levels, and occasional loss of HBsAg (5%) and HBeAg (16%) among participants with chronic hepatitis B on nucleos(t)ide analogue therapy with viral suppression. Our results support continued development of selgantolimod as a component of a future hepatitis B cure regimen.

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials.

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).

A retinal circuit for the suppressed-by-contrast receptive field of a polyaxonal amacrine cell.

Amacrine cells are a diverse population of interneurons in the retina that play a critical role in extracting complex features of the visual world and shaping the receptive fields of retinal output neurons (ganglion cells). While much of the computational power of amacrine cells is believed to arise from the immense mutual interactions among amacrine cells themselves, the intricate circuitry and functions of amacrine-amacrine interactions are poorly understood in general. Here we report a specific interamacrine pathway from a small-field, glutamate-glycine dual-transmitter amacrine cell (vGluT3) to a wide-field polyaxonal amacrine cell (PAS4/5). Distal tips of vGluT3 cell dendrites made selective glycinergic (but not glutamatergic) synapses onto PAS4/5 dendrites to provide a center-inhibitory, surround-disinhibitory drive that helps PAS4/5 cells build a suppressed-by-contrast (sbc) receptive field, which is a unique and fundamental trigger feature previously found only in a small population of ganglion cells. The finding of this trigger feature in a circuit upstream to ganglion cells suggests that the sbc form of visual computation occurs more widely in the retina than previously believed and shapes visual processing in multiple downstream circuits in multiple ways. We also identified two different subpopulations of PAS4/5 cells based on their differential connectivity with vGluT3 cells and their distinct receptive-field and luminance-encoding characteristics. Moreover, our results revealed a form of crosstalk between small-field and large-field amacrine cell circuits, which provides a mechanism for feature-specific local (<150 µm) control of global (>1 mm) retinal activity.

Learning Background-Suppressed Dual-Regression Correlation Filters for Visual Tracking.

The discriminative correlation filter (DCF)-based tracking method has shown good accuracy and efficiency in visual tracking. However, the periodic assumption of sample space causes unwanted boundary effects, restricting the tracker's ability to distinguish between the target and background. Additionally, in the real tracking environment, interference factors such as occlusion, background clutter, and illumination changes cause response aberration and, thus, tracking failure. To address these issues, this work proposed a novel tracking method named the background-suppressed dual-regression correlation filter (BSDCF) for visual tracking. First, we utilize the background-suppressed function to crop out the target features from the global features. In the training step, while introducing the spatial regularity constraint and background response suppression regularization, we construct a dual regression structure to train the target and global filters separately. The aim is to exploit the difference between the output response maps for mutual constraint to highlight the target and suppress the background interference. Furthermore, in the detection step, the global response can be enhanced by a weighted fusion of the target response to further improve the tracking performance in complex scenes. Finally, extensive experiments are conducted on three public benchmarks (including OTB100, TC128, and UAVDT), and the experimental results indicate that the proposed BSDCF tracker achieves tracking performance comparable to many state-of-the-art (SOTA) trackers in a variety of complex situations.

Learning Response-Consistent and Background-Suppressed Correlation Filters for Real-Time UAV Tracking.

With the advantages of discriminative correlation filter (DCF) in tracking accuracy and computational efficiency, the DCF-based methods have been widely used in the field of unmanned aerial vehicles (UAV) for target tracking. However, UAV tracking inevitably encounters various challenging scenarios, such as background clutter, similar target, partial/full occlusion, fast motion, etc. These challenges generally lead to multi-peak interferences in the response map that cause the target drift or even loss. To tackle this problem, a response-consistent and background-suppressed correlation filter is proposed for UAV tracking. First, a response-consistent module is developed, in which two response maps are generated by the filter and the features extracted from adjacent frames. Then, these two responses are kept to be consistent with the response from the previous frame. By utilizing the l2-norm constraint for consistency, this module not only can avoid sudden changes of the target response caused by background interferences but also enables the learned filter to preserve the discriminative ability of the previous filter. Second, a novel background-suppressed module is proposed, which makes the learned filter to be more aware of background information by using an attention mask matrix. With the introduction of this module into the DCF framework, the proposed method can further suppress the response interferences of distractors in the background. Finally, extensive comparative experiments have been conducted on three challenging UAV benchmarks, including UAV123@10fps, DTB70 and UAVDT. Experimental results have proved that our tracker has better tracking performance compared with 22 other state-of-the-art trackers. Moreover, our proposed tracker can run at ∼36 FPS on a single CPU for real-time UAV tracking.

Therapeutic strategy for atypical ulnar fracture in long use of bisphosphonate: A systematic review.

BACKGROUND: Atypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed. METHODS: A systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy. RESULTS: Forty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment. CONCLUSIONS: Based on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.

(E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment.

Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single-cell hub 2 website was used for graph-based visualization of Smad3 status in osteosarcoma single-cell database. Western Blot was applied to detect the expression of Smad3 protein in cell lines. Colony formation and cell counting kit-8 assays were used to evaluate cell proliferation. Transwell and wound healing assays were used to detect the migration and invasion abilities of cells. Cell apoptosis rates and cell cycle changes were explored by using flow cytometry analysis. The xenograft tumor growth model was applied to explore the effect in tumor growth after Smad3 blockage in vivo. Moreover, to confirm the potential mechanism of Smad3's effects on osteosarcoma, bioinformatics analysis was performed in TARGET-Osteosarcoma and GSE19276 databases. Our study found that the Smad3 protein is overexpressed in 143B and U2OS cells, suppressing the expression of Smad3 protein in osteosarcoma cells by Smad3 target inhibitor (E)-SIS3 or lentivirus can inhibit the proliferation, migration, invasion, promote cell apoptosis, arrest cell G1 cycle in osteosarcoma cells in vitro, and suppress tumor growth in vivo. Furthermore, the bioinformatics analysis demonstrated that high expression of Smad3 is closely associated with low immune status in TARGET-Osteosarcoma and GSE19276 databases. Our study suggested that Smad3 could contribute positively to osteosarcoma progression via the regulation of tumor immune microenvironment, and Smad3 may represent as an valuable potential therapeutic target in osteosarcoma therapy.

Enhancing Flame Retardancy and Smoke Suppression in Epoxy Resin Composites with Sulfur-Phosphorous Reactive Flame Retardant.

The presence of massive amounts of toxic volatiles and smoke during combustion is a very serious problem facing epoxy resin (EP) composites. Therefore, flame retardants (FRs) can simultaneously enhance flame retardancy and reduce the release of smoke and fatal gases. Herein, a novel sulfur-phosphorous reactive flame retardant (SPMS) was synthesized for epoxy resin. The high efficiency of smoke suppression and flame retardancy of the EP/SPMS-APP hybrid was investigated using a cone calorimeter, a vertical burning test, and limited oxygen index measurements. Compared with those of pure EP, the composite with 20 wt% SPMS-APP reduced the peak heat release rate (pHRR), the peak smoke production rate (SPR), and total smoke production rate (TSR) by 82%, 94%, and 84%, respectively. The results showed a remarkable suppressed effect of alleviating the fire hazard of EP using a sulfur-phosphorus flame retardant.

Suppressive Strong Metal-Support Interactions on Ruthenium/TiO2 Promote Light-Driven Photothermal CO2 Reduction with Methane.

Strong metal-support interactions (SMSI) have gained great attention in the heterogeneous catalysis field, but its negative role in regulating light-induced electron transfer is rarely explored. Herein, we describe how SMSI significantly restrains the activity of Ru/TiO2 in light-driven CO2 reduction by CH4 due to the photo-induced transfer of electrons from TiO2 to Ru. In contrast, on suppression of SMSI Ru/TiO2 -H2 achieves a 46-fold CO2 conversion rate compared to Ru/TiO2 . For Ru/TiO2 -H2 , a considerable number of photo-excited hot electrons from Ru nanoparticles (NPs) migrate to oxygen vacancies (OVs) and facilitate CO2 activation under illumination, simultaneously rendering Ruδ+ electron deficient and better able to accelerate CH4 decomposition. Consequently, photothermal catalysis over Ru/TiO2 -H2 lowers the activation energy and overcomes the limitations of a purely thermal system. This work offers a novel strategy for designing efficient photothermal catalysts by regulating two-phase interactions.