Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid ß-protein (Aß) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aß promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-ß1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-ß1 pathway and increased TGF-ß1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-ß1 in the disease process.

The diagnostic utility of CT attenuation values in detecting calcification within costal cartilage.

BACKGROUND: To establish and verify diagnostic criteria for the identification of costal cartilage calcification based on computed tomography (CT) attenuation value. METHODS: 360 chest CT slices of 120 patients were reviewed and annotated retrospectively and receiver operating characteristic curve was used to evaluate the diagnostic ability of CT attenuation value. Another 20 slices containing calcification were randomly selected and annotated by 4 doctors for further validation. hematoxylin and eosin and collagen type X (COLX) staining was performed on the residual costal cartilage. RESULTS: In total 355,129 voxels were detected and 187.5 was confirmed as the optimal CT attenuation value threshold, with a sensitivity of 98.6% and a specificity of 99.7%, for costal cartilage calcification diagnosis. Threshold-based identification of calcification demonstrated a similarity of nearly 80% with specialists' assessments, and exhibited advantages in the identification of subtle calcifications in the further validation. We also observed that CT attenuation values among males demonstrated a centralized distribution, whereas those among females exhibited a bimodal distribution. Threshold-based identified calcification showed a positivity of COLX. CONCLUSIONS: CT attenuation value could validly and reliably diagnose calcification within costal cartilage. Further investigations involving larger cohorts of patients are required to elucidate the risk factors and underlying mechanisms of costal cartilage calcification.

On-site burn severity assessment using smartphone-captured color burn wound images.

Accurate assessment of burn severity is crucial for the management of burn injuries. Currently, clinicians mainly rely on visual inspection to assess burns, characterized by notable inter-observer discrepancies. In this study, we introduce an innovative analysis platform using color burn wound images for automatic burn severity assessment. To do this, we propose a novel joint-task deep learning model, which is capable of simultaneously segmenting both burn regions and body parts, the two crucial components in calculating the percentage of total body surface area (%TBSA). Asymmetric attention mechanism is introduced, allowing attention guidance from the body part segmentation task to the burn region segmentation task. A user-friendly mobile application is developed to facilitate a fast assessment of burn severity at clinical settings. The proposed framework was evaluated on a dataset comprising 1340 color burn wound images captured on-site at clinical settings. The average Dice coefficients for burn depth segmentation and body part segmentation are 85.12 % and 85.36 %, respectively. The R2 for %TBSA assessment is 0.9136. The source codes for the joint-task framework and the application are released on Github (https://github.com/xjtu-mia/BurnAnalysis). The proposed platform holds the potential to be widely used at clinical settings to facilitate a fast and precise burn assessment.

Defect-Mediated Formation of Oriented Phase Domains in a Lithium-Ion Insertion Electrode.

The performance and robustness of electrodes are closely related to transformation-induced nanoscale structural heterogeneity during (de)lithiation. As a result, it is critical to understand at atomic scale the origin of such structural heterogeneity and ultimately control the transformation microstructure, which remains a formidable task. Here, by performing in situ studies on a model intercalation electrode material, anatase TiO2, we reveal that defects─both preexisting and as-formed during lithiation─can mediate the local anisotropic volume expansion direction, resulting in the formation of multiple differently oriented phase domains and eventually a network structure within the lithiated matrix. Our results indicate that such a mechanism operated by defects, if properly harnessed, could not only improve lithium transport kinetics but also facilitate strain accommodation and mitigate chemomechanical degradation. These findings provide insights into the connection of defects to the robustness and rate performance of electrodes, which help guide the development of advanced lithium-ion batteries via defect engineering.

Magnetic navigation-assisted colonoscopic enteral tube placement in swine (with video): a preliminary study.

BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

Synergistic Effect Between 0D CQDs and 2D MXene to Enhance the Photothermal Conversion of Hydrogel Evaporators for Efficient Solar Water Evaporation, Photothermal Sensing and Electricity Generation.

Solar-powered interfacial water evaporation is a promising technique for alleviating freshwater stress. However, the evaporation performance of solar evaporators is still constrained by low photothermal conversion efficiency and high water evaporation enthalpy. Herein, 0D carbon quantum dots (CQDs) are combined with 2D MXene to serve as a hybrid photothermal material to enhance the light absorption and photothermal conversion ability, meanwhile sodium carboxymethyl cellulose (CMC)/polyacrylamide (PAM) hydrogels are used as a substrate material for water transport to reduce the enthalpy of water evaporation. The synergistic effect in 0D CQDs/2D MXene hybrid photothermal materials accelerate the carrier transfer, inducing efficient localized surface plasmon resonance (LSPR) effect. This results in the enhanced photothermal conversion efficiency. The integrated hydrogel evaporators demonstrate a high evaporation rate (1.93 and 2.86 kg m-2 h-1 under 1 and 2 sunlights, respectively) and low evaporation enthalpy (1485 J g-1). In addition, the hydrogel evaporators are applied for photothermal sensing and temperature difference power generation (TEG). The TEG device presents an efficient output power density (230.7 mW m-2) under 1 sunlight. This work provides a feasible approach for regulating and controlling the evaporation performances of hydrogel evaporators, and gives a proof-of-concept for the design of multipurpose solar evaporation systems.

Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles.

Purpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4-8°C) likely influences the organism's blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM. Methods: The effects of CT (4-8°C) or room temperature (RT, 22-25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot. Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting ß-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect. Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.

Characterization and functional analysis of novel α-bisabolol synthase (MrBAS) promoter from Matricaria recutita.

Matricaria recutita is widely used in industry and as a medicinal plant because it contains α-bisabolol. Alpha-bisabolol has broad application prospects due to its healthy function and medical value. The activity of the α-bisabolol synthase (MrBAS) promoter determines the expression of the MrBAS gene, which in turn influences the synthesis and accumulation of α-bisabolol. However, the activity and tissue specificity of the MrBAS promoter have not yet been characterized. In this study, a 1327-base pair (bp) region upstream of the MrBAS of the translation start site was cloned from the genome of M. recutita. MrBAS promoter sequence analysis revealed multiple light-responsive elements, and further dark treatment reduced α-bisabolol content in flowers. The α-bisabolol content and MrBAS expression levels in various flower tissues showed a strong correlation. The 5' deletion analysis revealed that the MrBAS promoter sequence could drive ß-glucuronidase (GUS) gene expression in Nicotiana benthamiana leaves, with activity decreasing as the fragment shortened. Transgenic experiments demonstrated that the MrBAS promoter could specifically drive GUS gene expression in Arabidopsis anthers, pollen tubes, and petals. Thus, the MrBAS promoter has the potential to be a tool for directing transgene expression specifically in flower organs, offering new research avenues for cultivar development.

Multivariate Analysis and Prediction Model Construction for Dermatoscope Use by Chinese Dermatologists via an Online Survey.

BACKGROUND: The use of dermatoscopes is constantly increasing globally, but to date, there are no studies on the use of dermatoscopes by Chinese dermatologists. OBJECTIVE: To determine factors influencing the use of dermatoscopes in China. METHODS: A web-based questionnaire was designed by the Department of Dermatology at Huashan Hospital affiliated with Fudan University and was published online via the Shanghai Wheat Color Intelligent Technology Company, China. In 2019 and 2022, 1581 and 1507 dermatologists, respectively, were recruited and completed the questionnaire online. RESULTS: In China, the application rate of dermatoscopy is higher in eastern provinces than in western and remote areas. The proportion of doctors from public tertiary hospitals is the highest, with females being the majority. The age range of 30-40 years has the highest proportion, the proportion of doctors with professional titles of attending physician or above is the highest, and the proportion of doctors with a bachelor's degree or above is the highest. CONCLUSIONS: By improving the education and professional standards of doctors, providing more training opportunities, simplifying access, and promoting dermatoscopy in grassroots hospitals, we can increase the confidence of dermatologists in the use of dermatoscopy.

Effects and mechanisms of different exogenous organic matters on selenium and cadmium uptake by rice in natural selenium-cadmium-rich soil.

Many natural selenium (Se)-rich rice plants are being polluted by cadmium (Cd). In this study, for reducing Cd concentrations in rice grains while maintaining Se concentrations, the effects of different exogenous organic matters (OMs), such as humic acid (HA), cow manure (CM), and vermicompost (VC), on Se and Cd uptake in rice growing in natural Se-Cd-rich paddy soils were investigated by pot experiments. The Se and Cd concentrations in the soil solution, their species in the soil, and their concentrations and translocations in rice tissues were determined. Results showed that different exogenous OMs exhibited distinct percentage changes in Se and Cd levels in rice grains with amplitudes of -19.42 % and -56.90 % (significant, p < 0.05) in the HA treatments, +10.79 % and -1.72 % in the CM treatments, and +15.83 % and -15.52 % in the VC treatments, respectively. Correlation analysis showed that the concentrations of Se and Cd in rice grains might be primarily influenced by their concentrations in the soil solution, rather than the Se/Cd molar ratios in the soil solution or their translocations in rice tissues. HA decreased Se and Cd bioavailability in soil by increasing HA-bound Se and residual Cd, respectively. Meanwhile, HA increased soil solution pH, which was negative for Cd bioavailability but positive for Se bioavailability. This additive effect made HA lowered Cd concentration more than Se concentration in both soil solution and grain. CM and VC did not have this additive effect and thus have limited effects on grain Se and Cd concentrations. In addition, according to grain Se and Cd concentrations, to prioritize reducing Cd in rice, use HA; to prioritize increasing Se in rice, use VC. This study enhances the understanding of Se and Cd uptake mechanisms in rice with the applications of various OMs and offers potential remediation methods for Se-Cd-rich paddy soils.

Ring-extended carbazole modification to activate efficient phosphorescent OLED performance of traditional host materials.

A novel "Ring-expansion" strategy is proposed to optimize traditional host molecular structures, featuring a rigid molecular skeleton and excellent transport of carriers. Consequently, the two novel host materials facilitate the fabrication of efficient phosphorescent OLEDs with suppressed efficiency roll-off compared to OLEDs based on the conventional host material (mCP).

Minimally Invasive Combined Medial and Lateral Approach for Treating Displaced Scapular Body and Neck Fractures.

BACKGROUND Traditional open surgery for displaced scapular body and neck fractures often results in significant trauma and complications. This study aimed to assess the efficacy of a combined medial and lateral minimally invasive approach compared with the traditional Judet approach. MATERIAL AND METHODS A retrospective analysis was conducted on 36 patients (22 men, 14 women; mean age 45.6 years) with displaced scapular body and neck fractures treated between May 2016 and May 2022. Nineteen patients underwent the minimally invasive approach, while 17 received the traditional Judet approach. Primary outcomes included surgical incision length, intraoperative blood loss, complication rate, time to postoperative pain relief (VAS score ≤3), and Constant-Murley shoulder score at 12 months. Statistical analysis was done using the t test and chi-square test. RESULTS The minimally invasive group had shorter incision lengths (mean difference: 10.0 cm; 95% CI: 8.1-11.9; P<0.001) and lower blood loss (mean difference: 129.4 mL; 95% CI: 119.0-139.8; P<0.001). They also experienced faster pain relief (mean difference: 3.0 days; 95% CI: 2.5-3.5; P<0.001) and higher Constant-Murley scores (mean difference: 7.4 points; 95% CI: 4.9-9.9; P<0.001). There were no significant differences in operative duration or fracture healing time. CONCLUSIONS The combined medial and lateral minimally invasive approach offers superior outcomes in reducing incision length, blood loss, complications, and pain, with enhanced shoulder function, making it a safe and effective alternative to the traditional Judet approach.

3D cellulose scaffold with gradient pore structure controlled by hydrogen bond competition: Super-strength and multifunctional oil/water separation.

Cellulose-based aerogels offer exceptional promise for oily wastewater treatment, but the challenge of low mechanical strength and limited application functions persists. Inspired by the graded porous structures in the animal skeleton and bamboo stem, we firstly report here a stepwise solvent diffusion-induced phase separation approach for constructing the gradient pore-density three-dimensional (3D) cellulose scaffold (GPDS). Benefiting from the regulation of competitive hydrogen bonding between the anti-solvents and the ionic liquid (IL) in cellulose solution, GPDS exhibits the decreased major channels size and increased minor pores amount gradually along the solvent diffusion direction. These endow GPDS with the characteristics of low density (0.019 g/cm) and super strength (high up to 870 KPa). The application of GPDS in the field of oil-water separation has achieved remarkable results, including oil/organic solvent absorption (13-25 g/gGPDS), immiscible oil-water mixture separation (high efficiency up to 99.8 %, flux > 2000 L/m2·h), and surfactant-stabilized oil-in-water emulsion (efficiency up to 97.7 %). Moreover, a simple hydrophobic treatment further realizes the efficient separation of water-in-oil emulsion (98.5 % efficiency). The as-fabricated GPDS accordingly achieves the multifunctional application in oil-water separation field. Thus, a new avenue is opened to construct 3D cellulose porous scaffold as adsorbent materials in oily wastewater treatment.

Formation Characteristics of Pt-Ni Alloy Nanoparticles Fabricated by Nanolamination of Atomic Layer Deposition in Hydrogen.

Forced-flow atomic layer deposition nanolamination is employed to fabricate Pt-Ni nanoparticles on XC-72, with the compositions ranging from Pt94Ni6 to Pt67Ni33. Hydrogen is used as a co-reactant for depositing Pt and Ni. The growth rate of Pt is slower than that using oxygen reactant, and the growth exhibits preferred orientation along the (111) plane. Ni shows much slower growth rate than Pt, and it is only selectively deposited on Pt, not on the substrate. Higher ratios of Ni would hinder subsequent stacking of Pt atoms, resulting in lower overall growth rate and smaller particles (1.3-2.1 nm). Alloying of Pt with Ni causes shifted lattice that leads to larger lattice parameter and d-spacing as Ni fraction increases. From the electronic state analysis, Pt 4f peaks are shifted to lower binding energies with increasing the Ni content, suggesting charge transfer from Ni to Pt. Schematic of the growth behavior is proposed. Most of the alloy nanoparticles exhibit higher electrochemical surface area and oxygen reduction reaction activity than those of commercial Pt. Especially, Pt83Ni17 and Pt87Ni13 show excellent mass activities of 0.76 and 0.59 A mgPt -1, respectively, higher than the DOE target of 2025, 0.44 A mgPt -1.

Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS: Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.

Cellulose-based colorimetric/ratiometric fluorescence sensor for visual detecting amines and anti-counterfeiting.

Many amines with high toxicity always cause a serious threat to the ecological environment and human health; thus, their detection is important. Herein, a dual-mode colorimetric and ratiometric fluorescent sensor based on cellulose for detecting amines has been constructed by a new strategy. This sensor is made of a "negative response" indicator (Lum-MDI-CA) and a "positive response" indicator (perylene tetracarboxylic acid, PTCA). Lum-MDI-CA was obtained by attaching luminol onto cellulose chains, which emitted blue fluorescence and was quenched upon contact with amines. A possible mechanism of fluorescence quenching phenomenon is proposed by the intramolecular charge transfer (ICT) of Lum-MDI-CA. Subsequently, by simply mixing Lum-MDI-CA with PTCA, a dual-mode fluorescence sensor was designed for visual detection and classification of amines. When adding ammonia (NH3), morpholine (MOR), benzylamine (BNZ), diethylamine (DEA), and triethylamine (TEA), respectively, the dual-mode sensor showed visible different color changes under both UV light and daylight. In addition, owing to the excellent processibility and formability of cellulose acetate backbone, the prepared sensor can be easily processed into different material forms, including inks, coatings, films, and fibers, which still exhibit excellent fluorescence emission. Such sensors based on cellulose fluorescent materials are of great value in anti-counterfeiting and information encryption.

Exploring expression levels of the cGAS-STING pathway genes in peripheral blood mononuclear cells of spinal tuberculosis patients.

BACKGROUND: This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. METHODS: Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon ß (IFN-ß) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. RESULTS: The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-ß was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-ß was not statistically significant (P > 0.05), and the serum IFN-ß concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-ß in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively. CONCLUSIONS: The expression level of TBK1 and IRF3 in PBMCs, and IFN-ß in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-ß in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Direct Ink Writing of Liquid Metal on Hydrogel through Oxides Introduction.

Hydrogel-based flexible electronics have been widely investigated in electronic skin and wearable sensors. However, the challenge of matching the modulus between the hydrogel and the electrode underscores the critical importance of flexibility of the electrode. Gallium-based liquid metals (GaLMs) are ideal electrode materials for flexible substrates due to their high conductivity and stretchability. However, the ease of aggregation and lack of adhesion happen when patterning GaLMs on hydrogel surfaces. This work proposes a direct ink writing (DIW) of highly oxidized EGaIn (hoEGaIn) on an acrylamide (AAm) hydrogel. The interface is modulated by increasing the oxide content to improve the printability. Compared to EGaIn with an oxide layer, hoEGaIn displays a lower surface tension dropped by about 28.5%, higher adhesion (an increase of about 24.4%), and lower contact angles. These optimized interface properties significantly improve its wettability and DIW stability on AAm hydrogel substrates. A minimum line width of 65 µm is obtained by regulating DIW parameters. Meanwhile, hoEGaIn exhibits impressive multisubstrate printability and conductivity of up to 2.22 × 106 S·m-1. Furthermore, a cantilever beam strain sensor is manufactured by DIW hoEGaIn on an AAm hydrogel, which exhibits fast response and recovery, excellent dynamic response, and stability. This study demonstrates a potential method for the DIW of GaLMs on hydrogels.

Microstructure, Mechanical, and Tribological Properties of Nb-Doped TiAl Alloys Fabricated via Laser Metal Deposition.

TiAl alloys possess excellent properties, such as low density, high specific strength, high elastic modulus, and high-temperature creep resistance, which allows their use to replace Ni-based superalloys in some high-temperature applications. In this work, the traditional TiAl alloy Ti-48Al-2Nb-2Cr (Ti4822) was alloyed with additional Nb and fabricated using laser metal deposition (LMD), and the impacts of this additional Nb on the microstructure and mechanical and tribological properties of the as-fabricated alloys were investigated. The resulting alloys mainly consisted of the γ phase, trace ß0 and α2 phases. Nb was well distributed throughout the alloys, while Cr segregation resulted in the residual ß0 phase. Increasing the amount of Nb content increased the amount of the γ phase and reduced the amount of the ß0 phase. The alloy Ti4822-2Nb exhibited a room-temperature (RT) fracture strength under a tensile of 568 ± 7.8 MPa, which was nearly 100 MPa higher than that of the Ti4822-1Nb alloy. A further increase in Nb to an additional 4 at.% Nb had little effect on the fracture strength. Both the friction coefficient and the wear rate increased with the increasing Nb content. The wear mechanisms for all samples were abrasive wear with local plastic deformation and oxidative wear, resulting in the formation of metal oxide particles.

18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden.

Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27-176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08-0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08-0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm3 and 500 g, respectively. A prediction model combining maximum standardized uptake value (SUVmax) at 1 month after CAR-T cell therapy (M1) and tTLG clearance rate was established to predict early progression for partial response/stable disease patients evaluated at M1 after CAR-T cell therapy and validated in Lyon cohort. Relevant association of the distance separating the two farthest lesions, standardized by body surface area to the severity of neurotoxicity (AUC = 0.74; P = 0.034; 95% CI, 0.578-0.899) after CAR-T cell therapy was found in patients received axicabtagene ciloleucel. In patients with Dmax ≥ 6 cm, RNA-sequencing analysis conducted at the screening stage showed enrichment of immunosuppressive-related biological processes, as well as increased M2 macrophages, cancer-associated fibroblasts, myeloid-derived suppressor cells, and intermediate exhausted T cells. Collectively, immunosuppressive tumor microenvironment may serve as a negative prognostic indicator in patients with high tumor burden who respond poorly to CAR-T cell therapy.