Terminal transition-metal nitrides are key intermediates in dinitrogen activation and nitrogen-transfer chemistry and have therefore long attracted considerable attention. Despite the intensive work on Cr(V/VI) nitrides in the past, systematic investigations on Cr(IV) nitrides remain lacking. Herein, we report the synthesis and characterization of a Cr(IV) nitride, [Cp*CrIV(N)(depe)] (1, Cp* = C5Me5, depe = 1,2-bis(diethylphosphino)ethane), and its one-electron oxidized form, [Cp*CrV(N)(depe)]+ (2), using solid-state 15N nuclear magnetic resonance, electron paramagnetic resonance, and UV-vis spectroscopies coupled with density functional theory calculations. Our findings reveal that both species feature an overwhelming Cr≡N triple-bonding interaction that is yet considerably perturbed by the pronounced π-donating and π-accepting properties of the cyclopentadienyl and bisphosphine ligands, respectively. As a manifestation, Cr(IV) nitride 1 is distinguished by a rhombic 15N chemical shift tensor that is disparate from an axial one anticipated for a Cr≡N triple bond, because the Cr-to-depe π-backdonation lifts the 2-fold degeneracy of the Cr≡N π-bonding. Due to the presence of a low-lying LMCT excitation from the doubly occupied Cp* π-orbital to the singly populated Cr dx2-y2 orbital, Cr(V) nitride 2 exhibits an unprecedented g∥ > ge > g⊥ pattern for all d1 metal oxides and nitrides whose three g-components are otherwise constantly less than ge.
T cell receptors (TCRs) and TCR-mimicking antibodies recognize peptide antigens in the context of specific Human Leucocyte Antigen (HLA-I) allotypes, and the extreme polymorphism of the HLA locus limits the breadth of immunotherapy development. Key barriers include divergent molecular surfaces on HLA proteins and differences in the peptide structure. As a result, existing modalities cannot confer therapeutic coverage across patients of divergent genetic backgrounds. Here, we develop an approach which combines a peptide conformational prediction tool, PepPred, with a cross-HLA binding protein engineering system, TRACeR-I 1 , to outline a generalized framework for developing binders (xTRACeRs) with compatibility across HLA allotypes while maintaining high levels of specificity towards the peptide antigen. We use our system to develop and validate xTRACeRs against clinically relevant, established peptide antigens presented across common alleles within five HLA-A/B/C supertypes 2 . Cryo-EM structures of xTRACeR-pHLA complexes for an oncofetal antigen from PRAME and a neuroblastoma-specific peptide from PHOX2B reveal effective mechanisms to navigate polymorphic HLA surface residues, and extensive interactions with the peptide. We implemented these two xTRACeRs as Chimeric Antigen Receptor (CAR) T cells and demonstrated their potent killing efficacy and specificity. Overcoming restriction across HLA supertypes lifts a key barrier in HLA-targeted immunotherapy by expanding patient coverage.
The quantum anomalous Hall (QAH) effect enables dissipationless transport. However, known QAH materials rarely combine ferrovalley behavior with spin-valley locking, and Néel antiferromagnets remain largely unexplored in QAH platforms. Here, we propose a spin-valley locked QAH ferrovalley state in a MnSe/Pt2HgSe3 heterostructure. Néel-ordered MnSe induces spin-polarized bands in Pt2HgSe3 via magnetic proximity, while spin-orbit coupling lifts valley degeneracy, yielding valley-dependent gaps and a sizable QAH gap of ∼40 meV at charge neutrality. Unlike conventional QAH systems, spin-valley locking is preserved in the conduction band, producing a distinct topological phase. Chemical-potential tuning drives transitions to spin-polarized anomalous valley Hall and anomalous Hall states with opposite spin-valley responses. An out-of-plane electric field reverses the Berry curvature distribution between valleys, while the Chern number and spin-valley texture are strongly coupled to the Néel vector, establishing a tunable antiferromagnetic topological-valleytronic platform.
Light-matter interactions in frustrated Kagome metals provide a platform for investigating hidden quantum states, while the microscopic origin of non-equilibrium symmetry breaking remains under discussion. Here, spin-lattice coupling in RbV3Sb5 is found to induce rotational and time-reversal symmetry breaking through enhancement of a single-QM phonon mode. The resulting anisotropic lattice distortion lifts geometric frustration and stabilizes a non-equilibrium ferrimagnetic phase accompanied by an intrinsic anomalous Hall effect. The calculations further indicate that coherent phonon excitation can modulate symmetry under strong optical fields without requiring orbital antiferromagnetism or extrinsic perturbations. The induced spin polarization, together with spin-orbit coupling, generates finite Berry curvature in momentum space and modifies the topological electronic structure. These results provide insight into the interplay among spin, lattice, and charge degrees of freedom in non-equilibrium correlated states of Kagome materials and may be relevant for optically controlled spintronic functionalities.
Body mass strongly influences maximal strength, complicating comparisons across individuals of different sizes and sexes. Traditional ratio standards and fixed allometric exponents often fail to adequately reduce body-mass dependence. This study examined whether sex-specific regression-residual normalization derived from log-log allometric models could reduce body-mass dependence to non-significant residual variance across multiple resistance exercises within this sample. Strength data were obtained from 203 college-aged adults (133 males, 70 females) who performed one-repetition maximum (1RM) tests for the bench press, squat, deadlift, snatch, clean and jerk, and overhead press, along with a 90-s one-arm kettlebell snatch test. Sex-specific allometric models of the form ln(P) = ln(a) + b·ln(M) were fitted for each exercise. Standardized residuals (W-scores) were calculated as size-adjusted performance indices. Normalization effectiveness was evaluated using correlations and regression slopes relating body mass to both raw performance and W-scores. Raw strength performance was positively associated with body mass across all barbell lifts (males: r = 0.25-0.44; females: r = 0.37-0.50; all p ≤ 0.010; R² ≈ 0.06-0.25). After normalization, associations between body mass and W-scores were reduced to near zero (males: r = - 0.06 to 0.01; females: r = - 0.02 to - 0.01; all p ≥ 0.48). Regression slopes were close to zero, and 95% confidence intervals included zero across all tasks. Sex-specific regression-residual normalization based on log-log allometric modeling reduced statistical body-mass dependence to negligible levels across diverse strength tasks within this sample. By emphasizing statistical independence of the normalized outcome, this approach provides a statistical framework for generating size-adjusted strength metrics for within-sample comparisons.
Numerous procedures have been described to lift breast tissue and to improve aesthetic appearance of the upper pole through auto-augmentation mastopexy procedures, with a wide range of techniques. This study introduces a novel mastopexy procedure designed to optimize volume in the central and upper breast pole using a mushroom-shaped flap. This article presents a modified approach to fill the breast's upper pole using a median, deep-based pedicle flap. This is a retrospective, multicentered study, based on a series of cases conducted by the author. The perioperative management and the surgical technique are described. A systematic approach was used to identify acute and subacute complications during the postoperative follow-up period. From January 2018 to December 2023, 198 women were included in the study and underwent mushroom mastopexy with or without implant and/or lipofilling. The mean age was 44.3 years (range, 18-74 y). The general complication rate was 13%, and we observed 1 hematoma that required reintervention. In 17 patients, local surgical revision was necessary due to hypertrophic scarring and nipple asymmetry. No nipple-areola complex necrosis was observed. Mushroom mastopexy lifts the breast while restoring maximum volume to the upper pole and can be combined with breast augmentation using implants or lipofilling. This technique is simple, reliable, and produces excellent aesthetic results with a low complication rate.
Colorectal cancer (CRC) represents a significant global health challenge, with early detection and minimally invasive treatments playing key roles in reducing morbidity and mortality. Endoscopic mucosal resection (EMR) is widely employed for flat colonic lesions, and the quality of submucosal elevation is a decisive factor for achieving complete resections, minimizing complications, and ensuring accurate histopathological assessment. Conventional 0.9% saline with dye is the standard solution but dissipates rapidly, while viscoelastic agents such as Blue Eye may offer more durable and technically advantageous lifts. This study aimed to compare the technical and histopathological outcomes of Blue Eye versus 0.9% saline with indigo carmine in EMR of flat colonic lesions, focusing on lateral margins, injection volume, procedural performance, and clinical safety. A prospective, single-center, triple-blind study was conducted between January and October 2024, including 14 patients undergoing 19 EMRs for Paris 0-IIa flat colonic lesions sized 20-30 mm. Patients were randomized to receive either Blue Eye or saline with indigo carmine. Baseline demographics, comorbidities, lesion features, procedural variables, and histopathological outcomes were collected. Statistical analysis included the Mann-Whitney test for continuous variables and Fisher's exact test for categorical data, adopting P<0.05 as significant. Baseline characteristics were comparable between groups regarding age, sex, and comorbidities. Blue Eye demonstrated significantly larger lateral margins (2.61±1.19 mm vs 1.81±0.37 mm, P=0.047) and required lower injection volume (4.60±1.50 mL vs 10.00±7.21 mL, P=0.020). Other variables, including procedure time, en bloc resection rate, bleeding, and number of clips, did not differ significantly. Anatomical lesion distribution and unfavorable anatomical findings also showed no statistical association with the solution employed. Blue Eye appears to provide superior technical performance in EMR of flat colonic lesions by ensuring wider lateral margins with less injection volume, without increasing adverse outcomes. Larger multicenter studies are needed to confirm and generalize these findings. O câncer colorretal (CCR) representa um desafio significativo para a saúde global, com a detecção precoce e os tratamentos minimamente invasivos desempenhando papéis fundamentais na redução da morbidade e mortalidade. A ressecção endoscópica da mucosa (RME) é amplamente empregada para lesões colônicas planas, e a qualidade da elevação da submucosa é um fator decisivo para alcançar ressecções completas, minimizar complicações e garantir uma avaliação histopatológica precisa. A solução salina convencional a 0,9% com corante é a solução padrão, mas se dissipa rapidamente, enquanto agentes viscoelásticos como o Blue Eye podem oferecer elevações mais duráveis e tecnicamente vantajosas. Este estudo teve como objetivo comparar os resultados técnicos e histopatológicos do Blue Eye versus solução salina a 0,9% com índigo carmim na RME de lesões colônicas planas, com foco nas margens laterais, volume de injeção, desempenho do procedimento e segurança clínica. Um estudo prospectivo, unicêntrico e triplo-cego foi conduzido entre janeiro e outubro de 2024, incluindo 14 pacientes submetidos a 19 EMRs para lesões colônicas planas Paris 0-IIa medindo 20-30 mm. Os pacientes foram randomizados para receber Blue Eye ou solução salina com índigo carmim. Dados demográficos basais, comorbidades, características da lesão, variáveis do procedimento e desfechos histopatológicos foram coletados. A análise estatística incluiu o teste de Mann-Whitney para variáveis contínuas e o teste exato de Fisher para dados categóricos, adotando p < 0,05 como significativo. As características basais foram comparáveis entre os grupos em relação à idade, sexo e comorbidades. Blue Eye demonstrou margens laterais significativamente maiores (2,61±1,19 mm vs 1,81±0,37 mm, P=0,047) e exigiu menor volume de injeção (4,60±1,50 mL vs 10,00±7,21 mL, P=0,020). Outras variáveis, incluindo tempo de procedimento, taxa de ressecção em bloco, sangramento e número de clipes, não diferiram significativamente. A distribuição anatômica da lesão e os achados anatômicos desfavoráveis também não mostraram associação estatística com a solução empregada. Blue Eye parece fornecer desempenho técnico superior em EMR de lesões colônicas planas, garantindo margens laterais mais amplas com menos volume de injeção, sem aumentar os resultados adversos. Estudos multicêntricos maiores são necessários para confirmar e generalizar esses achados.
The Silhouette InstaLift™ (Sinclair Pharma, Irvine, California, United States) has gained popularity as a minimally invasive technique with an effective and safe profile, offering immediate results and minimal downtime compared to barbed suture thread lifting. This study introduces a modified Silhouette InstaLift™ technique designed to enhance precision in thread placement and reduce complications. We report our experience on the clinical outcomes and safety of this modified technique. We retrospectively analyzed 100 consecutive cases treated between 2018 and 2023. All procedures were performed by a single surgeon using the modified Silhouette InstaLift™ technique. The approach involved precise thread placement and multi-point fixation to enhance the stability of the lift. Outcomes were assessed using the Global Aesthetic Improvement Scale (GAIS) at postoperative day 1, one month, three months, and six months. Complications were recorded and analyzed. The mean thread count used was 6.1±2.3. A small proportion of patients (7%) utilized other types of threads, and 3% underwent concurrent procedures. Complications were minimal, with 6% of patients experiencing dimples and 2% reporting unevenness. GAIS assessments showed that 90% of patients reported improvement on post-procedural day 1, which increased to 94% by six months. The trend demonstrated a sustained and even a continuous increase in aesthetic improvement over time. The modified Silhouette InstaLift™ technique provides enhanced precision in lifting, resulting in improved aesthetic outcomes and a lower complication rate. It can prevent cheekbone protrusion, provides greater stability than the original method, and leads to long-term satisfaction. Further research with larger and more diverse populations is recommended to validate this novel approach and explore long-term outcomes.
(1) Background: The role of baseline humoral immunization in bone regeneration remains unclear. This study assessed the relationship between baseline serological immunization, graft type, photobiomodulation (PBM), and histological outcomes after maxillary sinus floor augmentation. (2) Methods: This exploratory secondary analysis included 20 adults undergoing lateral maxillary sinus lifting. Patients were allocated according to graft type (allogeneic or xenogeneic) and postoperative protocol (with or without adjunctive PBM). Before surgery, serum samples were analyzed for anti-HLA class I, anti-HLA class II, and anti-MICA antibodies. After approximately 6 months, bone core biopsies were collected. Histological evaluation focused on inflammatory cell infiltrates (ICI). (3) Results: Baseline antibody positivity was detected in 35.0% of patients for anti-HLA class I, 55.0% for anti-HLA class II, and 45.0% for anti-MICA. Histological findings were generally favorable. ICI scores were low, with 65.0% of samples scoring 0 and 35.0% scoring 1. A nominal positive correlation was observed between anti-HLA class I NBG ratio and ICI; however, this finding did not remain statistically significant after correction for multiple comparisons. Exploratory PBM subgroup estimates were directionally different but were based on very small subgroups and should not be interpreted as evidence of effect modification. (4) Conclusions: The findings suggest a possible hypothesis-generating link between baseline humoral sensitization and mild local inflammatory infiltrates, which requires validation in larger, prospectively powered studies with predefined histological and immunological endpoints.
Though sinus floor augmentation surgery has been a well-established treatment modality for bone augmentation in the posterior maxilla, the effect of sinus membrane inflammation and sinus dimensions on graft maturation has not been elucidated. The purpose of this study was to evaluate the impact of sinus membrane thickness and sinus dimensions on the effectiveness of two graft materials-demineralized freeze-dried bone (DFDB) and bovine bone graft in sinus bone augmentation. Twenty patients requiring sinus floor augmentation surgery who had residual bone height less than 4 mm and ridge width of at least 5 mm were included in this randomized control study. All patients underwent a preoperative CBCT to determine the following-residual bone height, sinus width at a distance of 15 mm from the residual sinus floor, and the sinus membrane thickness. A two-stage procedure was opted for all the patients. Direct sinus lift was performed using the lateral window technique. Once the sinus membrane was lifted, patients were randomly allocated to one of the two groups, Group A-DFDB and Group B-Bovine bone graft. The second stage procedure of dental implant placement was carried out after six months. A statistically significant difference (p = .009) was seen between the groups for an average loss of bone graft by resorption. The mean was 4.38 mm ± 2.877 in Group A, and 1.58 ± 0.945 in Group B. Also, the bone height gained after 6 months in groups A and B was 8.52 mm ± 2.99 and 11.42 mm ± 0.94, respectively (p = .009).Further, on subgroup analysis, the mean graft resorption was 7.45 mm ± 1.593 when sinus membrane thickness was > 5 mm and it was 2.33 mm ± 0.903 when the membrane thickness was < 5 mm in Group A (p = .001). No statistically significant association could be derived for Group B in terms of immediate height gain, and mean bone loss for the sinus width and sinus membrane thickness variables, respectively. The average sinus width and sinus membrane thickness < 5 mm provide favorable anatomy for achieving acceptable bone height and lesser resorption after grafting with DFDB. However, when sinus membrane thickness is > 5 mm, bovine bone graft provides more predictable results.
The aging process is associated with various physiological changes, including declines in muscle strength and mass, which can reduce mobility and increase the risk of falls. Strength training is the most widely recognized strategy for enhancing muscle mass, strength, and function in older adults. Strength training with unstable equipment requires high levels of motor control and the generation of muscle strength. To test this assumption, this study compares the effects of a free-weight and an elastic-band strength-training program on functional performance. Forty-eight participants (67.1 ± 5.32 years; 28 men, 20 women) were randomized into three groups: a free-weight group (FWG, n = 16), an elastic band group (EBG, n = 17), and a control group (CG, n = 15). They completed 12 weeks of progressive resistance training, twice a week, with five main exercises designed to strengthen the entire body. Changes in strength were assessed using the 1-repetition maximum (1-RM) on the chest press and leg press. Functional performance was assessed using the following tests: climbing stairs, lifting and setting down a heavy box, the 30-second chair stand test, and the timed up-and-go test (TUG). Both the FWG and EBG demonstrated significant percentage improvements in the climbing stairs test (11.4 vs. 11.5%; p = .013), 30s chair test (10.2 vs. 19.8%; p = .044), box lift (31.8 vs. 44.8%; p < .001), and TUG with bags fast (7.1 vs. 11.1%; p = .011), but not for chest press (7.3% vs. 3.6%; p = .184) and leg press (16.8% vs. 23.9%; .p = .322) compared to the CG. The findings of this study suggest that resistance training adaptations exhibit high task specificity in older adults, and significant improvements in functional outcomes can be achieved with elastic bands.
Resistance training remains underused in the rehabilitation of children with neurodevelopmental disorders, despite growing evidence of its multidimensional benefits beyond muscular strength. This case describes how an adapted resistance exercise program appeared to support functional, behavioral, and emotional changes in a child with developmental delay secondary to perinatal hypoxic brain injury. A 13-year-old girl of European descent with global developmental delay following perinatal cervical trauma and hypoxic brain injury, studying in a specialized educational institution, participated in a 12-week individualized resistance training program. Sessions were held 3 times per week for 45-60 min, depending on her concentration and tolerance. Exercises included bodyweight squats while holding on to wall bars (stall bars), knee push-ups, assisted abdominal crunches with leg fixation, and pull-ups on an inclined rehabilitation board (Evminov board), all tailored to her abilities and closely supervised. Her communication was limited to a few words and gestures, and she presented with impulsive behavior, poor motor control, and sensory processing difficulties. After 12 weeks, she showed observable improvements in posture, gait stability, endurance, and engagement during physical tasks. Teachers and caregivers also noted reduced irritability, better emotional regulation, and more consistent participation in group activities. This case illustrates the feasibility and potential benefit of integrating individualized resistance training into rehabilitation programs for children with developmental disabilities. Such low-cost, simple interventions may complement standard therapies and enhance well-being in institutional or school settings. These observations are based on qualitative reports and should be interpreted with caution.
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by gradual progression. A significant pathophysiology of its development and evolution is neuroinflammation. A previous review assessed the neuroinflammation research in PD, but limitations in its search period and analytical methods restricted its ability to reflect the full landscape of the field and recent research trends. To solve this problem, we performed a bibliometric and visual review in order to describe the current state of research and outline the recent progress in PD-related neuroinflammation. The Web of Science Core Collection (WoSCC) and Scopus were searched to retrieve a total of 5,926 publications published between January 1, 2015 and September 23, 2025. CiteSpace, VOSviewer, and the bibliometrix R package were used to perform a comprehensive bibliometric and visualization analysis. The results showed that China produced the largest number of publications in this field, accounting for 30.75% of the total. At the institutional level, the University of California System and Shanghai Jiao Tong University were among the leading contributors. The International Journal of Molecular Sciences was the most productive journal in this field. Among individual authors, Wang, Q.S. Zhang, F. and Cuzzocrea, S. were the most prolific contributors, whereas McGeer, P.L. was the most frequently co-cited author. Keyword analysis further identified three major research themes: fundamental pathological mechanisms, clinical diagnosis, and intervention strategies. Overall, this study provides a systematic overview of the current research landscape, principal themes, and emerging directions in neuroinflammation research on PD by means of bibliometric analysis.
Sepsis often has a dysregulated inflammatory response and is accompanied by cardiac dysfunction. This study aimed to explore the mechanism of long non-coding RNA MIR503HG (MIR503HG) in regulating sepsis and the inflammatory responses, and sepsis-induced cardiac dysfunction (SICD). 102 sepsis patients were divided into an SICD group (n = 31) and a non-SICD group (n = 71). A cecal ligation and puncture (CLP) sepsis rat model was constructed. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the target gene expression. Enzyme-linked immunosorbent assay was used to measure the levels of myocardial damage markers and inflammatory factors. RNA immunoprecipitation and Dual luciferase assay were used to determine the targeting relationship. Kyoto Encyclopedia of Genes and Genomes analysis was used to predict signaling pathways of target genes. MIR503HG expression was significantly down-regulated in sepsis patients and SICD patients, and it has good diagnostic value for these two types of diseases. Its expression was significantly negatively correlated with myocardial injury markers (cardiac troponin I [cTnI], creatine kinase-MB [CK-MB]), cardiac function indicators (left ventricular ejection fraction), inflammatory factors (interleukin-6, tumor necrosis factor-alpha), and disease severity scores (Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II). Furthermore, it exerted a protective effect in sepsis: MIR503HG overexpression could effectively alleviate SICD and mitigate the inflammatory response, as evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure, reduced levels of CK-MB and cTnI, as well as restored myocardial systolic/diastolic capacity (maximal rate of left ventricular pressure rise/fall [±dP/dt]). Mechanistically, MIR503HG functions as a molecular sponge that sequesters microRNA-497-5p (miR-497-5p), thereby lifting brain-derived neurotrophic factor (BDNF). Delivery of miR-497-5p-agomiR partially offset the cardioprotective and anti-inflammatory effects of MIR503HG, whereas overexpression of BDNF partially restored them. MIR503HG relieved sepsis and reduced cardiac dysfunction and inflammatory response by regulating the miR-497-5p/BDNF axis.
Background: Mycoplasma pneumoniae (MP) is an important pathogen responsible for community-acquired respiratory infections in children. Global surveillance during the COVID-19 pandemic revealed a marked decline in MP activity. However, beginning in early summer 2023, multiple regions across China reported an unexpected resurgence of MP infections, highlighting the need for detailed epidemiological analysis. Objective: This study aimed to characterize the epidemiological features of MP seropositivity among children in Chengdu, southwest China, and to compare its patterns between the COVID-19 pandemic and post pandemic periods. Methods: A retrospective analysis was conducted on MP testing data from 39,552 children with acute respiratory infections who were treated at West China Second University Hospital, Sichuan University, between January 2022 and December 2023. Results: Both the number of MP tests conducted and the seropositivity rate were significantly lower during the pandemic period than during the post pandemic phase. Compared with male children, female children were more susceptible to MP seropositivity. In terms of age distribution, seropositivity rates were highest among toddlers (1-3 years) and school-aged children (6-14 years). During the pandemic period (2022), MP antibody-positive cases were observed mainly between January and July, whereas in the post pandemic phase (2023), the epidemic peak shifted from June to December. Conclusions: In this single-centre study in Chengdu, nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic was associated with a marked reduction in MP transmission. After these restrictions were lifted, a rebound in MP antibody positivity was observed among children in Chengdu, compared to the NPI period (2022), the post-NPI period (2023) showed a later seasonal peak, which may represent a delayed return to pre-pandemic patterns. Continuous strengthening of MP surveillance is necessary to provide early warning of potential resurgences and outbreak risks.
The renin-angiotensin system (RAS) contributes to inflammatory and neuropathic pain, but whether its primary receptors, AT1R and AT2R, regulate the K2P channel TWIK1 in sensory neurons remains unknown. We investigated whether Ang-II receptors modulate TWIK1 expression and whether this pathway influences neuropathic pain. Adult female rats underwent chronic constriction injury (CCI) of the sciatic nerve and received continuous subcutaneous administration of vehicle, telmisartan (AT1R antagonist), PD123319 (AT2R antagonist), or their combination for 14 days. TWIK1, AT1R, and AT2R expression were analyzed in dorsal root ganglia (DRG) by immunohistochemistry and RT-qPCR. Behavioral outcomes included spontaneous foot lifting, cold allodynia, and mechanical hypersensitivity. Plasma cytokines were quantified by ELISA. Satellite glial cell (SGC) activation was assessed via GFAP immunoreactivity. In vitro DRG cultures were exposed to inflammatory stimuli to evaluate TWIK1 transcriptional regulation. CCI reduced TWIK1 expression in DRG neurons, accompanied by dynamic regulation of AT1R and AT2R. Pharmacological blockade, particularly combined receptor inhibition, restored or increased TWIK1 expression, attenuated mechanical and cold hypersensitivity, reduced circulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and decreased SGC activation. Inflammatory stimulation in vitro reduced TWIK1 mRNA, supporting cytokine-mediated regulation. AT1R and AT2R regulate TWIK1 expression in sensory neurons through an integrated mechanism involving inflammatory signaling and glial activation. Dual receptor blockade produces the most consistent molecular and behavioral effects, supporting RAS modulation as a potential strategy for neuropathic pain management.
The design of soft actuators remotely controlled by optical triggering and propelling schemes requires materials that might combine ease of device fabrication and miniaturization with robust performance of moving parts and versatile and precise response to light stimuli. Here, light-triggered photochromic-doped poly(methyl methacrylate)/reduced graphene-oxide bilayers are proposed as effective actuation architectures, showing multi-photoaddressable bending and distinctive photothermal properties. By interlayer thermomechanical contrast and intrinsic mechanical amplification of photoinduced strain mismatch, these hybrid systems show good bending and load-lifting performance, broadband photothermal triggering, as well as faster thermal and actuation response compared to pristine photochromic films. Under UV illumination, measured displacements, exerted force, and response time reach values of about 200 μm, 2 mN, and the scale of few seconds, respectively. The photothermal conversion efficiency of the system is estimated to be at least 55%. Such properties make these architectures appealing as actuation elements for various device platforms, including segments of biomimetic components, and biomedical devices with precise structure-function design of the optical control.
To examine whether resistance training is associated with lower all-cause and cause-specific mortality, the dose-response relationship, and joint effects with aerobic activity. We included participants from three large prospective cohorts (Health Professionals Follow-up Study, 1992-2022; Nurses' Health Study, 2002-2021; Nurses' Health Study II, 2003-2021). Weekly resistance training duration and aerobic exercise duration were assessed using validated questionnaires at baseline and biennially thereafter. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Among 147 374 participants (31 540 men and 115 834 women) followed for up to 30 years, we documented 35 798 deaths. Compared with no resistance training, 90-119 min/week of resistance training was associated with a 13% lower risk of all-cause mortality (HR 0.87, 95% CI 0.81 to 0.95), 19% lower risk of cardiovascular mortality (HR 0.81, 95% CI 0.67 to 0.97) and 27% lower risk of neurological disease mortality (HR 0.73, 95% CI 0.58 to 0.92), adjusting for aerobic activity. No additional benefit was observed above 120 min/week. Reduced cancer mortality risk was seen only at lower levels of resistance training: HR 0.91 (95% CI 0.86 to 0.97) for 1-29 min/week and HR 0.88 (95% CI 0.81 to 0.97) for 30-59 min/week. In joint analyses, compared with those with inadequate aerobic activity (<7.5 metabolic equivalent of task (MET)-hours/week) and no resistance training, mortality risk was lowest among participants with both high aerobic and resistance training (eg, HR 0.55 (95% CI 0.50 to 0.60) for 30 to <45 MET-hours/week of aerobic and 60-119 min/week of resistance training), as well as among those attaining ≥45 MET-hours/week of aerobic activity regardless of resistance training level (HRs from 0.53 to 0.58). Using repeated measures of resistance training over up to 30 years of follow-up, moderate long-term resistance training was associated with lower all-cause mortality, with lowest risks plateauing at around ≥120 min/week of resistance training. Resistance training was associated with further reduced mortality risk at all levels of aerobic activity up to around ≥45 MET-hours/week of aerobic activity.
Spatial transcriptomics data are frequently compromised by technical artifacts, such as dry patches, tissue lifting, and uneven reagent coverage, which manifests as regions with low UMI counts, in particular at tissue borders. It can often be challenging to identify these regions using existing quality control methods. Here, we present SpatialArtifacts , a framework that combines median absolute deviation (MAD)-based outlier detection with mathematical morphology operations to identify and classify spatially contiguous tissue artifacts. Focal operations including 3×3 fill, 5×5 outline, and star-pattern connectivity link low-quality spots while preserving true biological domains. We use a hierarchical classification system to distinguish edge versus interior artifacts and large versus small regions, enabling downstream removal or targeted manual review. We demonstrate the performance of our method in human hippocampus, dorsolateral prefrontal cortex, and colorectal cancer tissues using 10x Genomics Visium and VisiumHD platforms. Our SpatialArtifacts package is freely available on Bioconductor at https://bioconductor.org/packages/SpatialArtifacts and on PyPI at https://pypi.org/project/spatial-artifacts/ .
Many materials, including those containing platinum group elements and noble metals, form nanometer-thick plates (nanoplates) in a range of natural environments, including ore deposits and serpentinites. Materials research uses metallic nanoplates, such as 2D metal oxide/sulfide in applications ranging from superconductors to biomedical engineering, because of their unique properties. A few techniques with sufficient spatial resolution can analyze these nanomaterials, such as nano-secondary ion mass spectroscopy. An alternative is atom probe tomography (APT), which provides in situ major and trace element data with nanometer-scale resolution and can analyze nanoplates. This research describes a novel method to produce APT samples from geological nanoplates using focused ion beam (FIB) lift-out. The redeposited material is used to fill voids at the interface between the plate and the substrate, consolidating the wedge that is lifted out for analysis. A case study of APT specimen preparation from a ∼500-nm-thick FeS plate, separated from an olivine substrate, by voids, ≤20 µm3 in volume, is described. The method produces robust specimens that yield millions of atoms during APT analysis. This method can be applied to nanoplates of different compositions and thicknesses from a broad range of materials, and to free-standing films supported by window structures.