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Nan Ding,1 Mei Luo,2 Ya-Hui Wen,3 Rong-Yin Li,1 Qi-Yan Bao1 1Department of Stomatology, Beijing LuHe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Central Laboratory, Beijing LuHe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Department of Internal Medicine, Beijing LuHe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of ChinaCorrespondence: Nan DingDepartment of Stomatology, Beijing LuHe Hospital, Capital Medical University, No. 82 of Xinhua South Road, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel/Fax +86 10 69543901Email dingnanstm16@163.comObjective: The present study aims to evaluate the effects of basic periodontal disease therapy on the general condition and serum inflammatory indicators of patients with rheumatoid arthritis (RA) combined with chronic periodontitis (CP).Methods: Forty patients with RA were enrolled in the study and, based on the results of an oral examination and in line with the 2018 periodontitis diagnostic criteria, they were divided into a group with CP (the RA + CP group) and a group without CP (the RA group). Twenty-nine patients with CP who attended the periodontal department of our hospital were recruited as a group with only CP (the CP group), and 20 volunteers without any systemic or periodontal disease were recruited as a healthy control group (the H group). The periodontal and joint conditions of the subjects in the four groups were recorded; anti-cyclic citrullinated protein antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and rheumatoid factor levels, which reflect the severity of the RA, were detected, and the differences between the groups were analyzed. The probing depth (PD), clinical attachment loss, and sulcus bleeding index (SBI), which reflect the severity of the periodontitis, were correlated with the factor levels. The RA + CP and CP groups received therapeutic intervention, and the differences in each indicator before and six weeks after the treatment were compared, and their data were compared with those of patients in the RA group and H groups.Results: Compared with the RA group, the serum expressions of ESR, CRP, and IL-6 were significantly higher in the RA + CP group. There were significant differences in the levels of PD, SBI, IL-6, and CRP in the patients receiving basic periodontal disease therapy before and after the treatment.Conclusion: A relatively large proportion of patients with RA have chronic periodontitis, and the local inflammatory state of CP might exacerbate the systemic inflammatory response in RA. Basic periodontal disease therapy may improve the oral condition of patients with RA and reduce the serum levels of the inflammatory factors.Keywords: chronic periodontitis, rheumatoid arthritis, citrullination, C-reactive protein, basic periodontal disease therapy, interleukin 6

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction., (© 2024 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Chiral tetrasubstituted allenes have emerged as important architectures for engineering biologically active compounds. The construction of unique tetrasubstituted allene scaffolds with precise control of continuous central and axial chirality remains yet to be developed. Here, we report a remote enantioselective ϵ-alkylation of yne-propargylic acetates with enals enabled by NHC and copper cooperative catalysis, leading to a series of tetrasubstituted allenes with excellent enantioselectivities (up to >99 % ee) and diastereoselectivities (up to >95 : 5 dr). This method features high regioselectivity and simultaneous control of axial and central chirality. Mechanistic studies suggest a cooperative activation mode and synergistic control of distal chirality created from the copper ethynylallenylidenes., (© 2024 Wiley-VCH GmbH.)

Objective: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22)., Design: A prospective cross-sectional study., Setting: The rhinology ward at our institution, a tertiary hospital., Participants: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires., Main Outcome Measures: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22., Results: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists., Conclusion: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30., (© 2024 John Wiley & Sons Ltd.)

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of Co N ( N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e. , Co 13 , Co 19 , Co 22 , Co 39 , and Co 43 , were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

The reconstruction of indoor scenes from multi-view RGB images is challenging due to the coexistence of flat and texture-less regions alongside delicate and fine-grained regions. Recent methods leverage neural radiance fields aided by predicted surface normal priors to recover the scene geometry. These methods excel in producing complete and smooth results for floor and wall areas. However, they struggle to capture complex surfaces with high-frequency structures due to the inadequate neural representation and the inaccurately predicted normal priors. This work aims to reconstruct high-fidelity surfaces with fine-grained details by addressing the above limitations. To improve the capacity of the implicit representation, we propose a hybrid architecture to represent low-frequency and high-frequency regions separately. To enhance the normal priors, we introduce a simple yet effective image sharpening and denoising technique, coupled with a network that estimates the pixel-wise uncertainty of the predicted surface normal vectors. Identifying such uncertainty can prevent our model from being misled by unreliable surface normal supervisions that hinder the accurate reconstruction of intricate geometries. Experiments on the benchmark datasets show that our method outperforms existing methods in terms of reconstruction quality. Furthermore, the proposed method also generalizes well to real-world indoor scenarios captured by our hand-held mobile phones. Our code is publicly available at: https://github.com/yec22/Fine-Grained-Indoor-Recon.

The chemical and physical properties of nanomaterials ultimately rely on their crystal structures, chemical compositions and distributions. In this paper, a series of AuCu bimetallic nanoparticles with well-defined architectures and variable compositions has been addressed to explore their thermal stability and thermally driven behavior by molecular dynamics simulations. By combination of energy and Lindemann criteria, the solid-liquid transition and its critical temperature were accurately identified. Meanwhile, atomic diffusion, bond order, and particle morphology were examined to shed light on thermodynamic evolution of the particles. Our results reveal that composition-dependent melting point of AuCu nanoparticles significantly departs from the Vegard's law prediction. Especially, chemically disordered (ordered) alloy nanoparticles exhibited markedly low (high) melting points in comparison with their unary counterparts, which should be attributed to enhancing (decreasing) atomic diffusivity in alloys. Furthermore, core-shell structures and heterostructures demonstrated a mode transition between the ordinary melting and the two-stage melting with varying Au content. AuCu alloyed nanoparticles presented the evolution tendency of chemical ordering from disorder to order before melting and then to disorder during melting. Additionally, as the temperature increases, the shape transformation was observed in AuCu nanoparticles with heterostructure or L1 0 structure owing to the difference in thermal expansion coefficients of elements and/or of crystalline orientations. Our findings advance the fundamental understanding on thermodynamic behavior and stability of metallic nanoparticles, offering theoretical insights for design and application of nanosized particles with tunable properties.

Aim: The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis., Methodology: We established an apical periodontitis mouse model in Sting -/- and WT mice in vivo. The progression of apical periodontitis was analysed by micro-CT analysis and H&E staining. The expression level and localization of STING in F4/80 + cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C-176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C-176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro-CT. Bone marrow-derived macrophages (BMMs) were isolated from Sting -/- and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C-176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast-related genes were tested using qRT-PCR., Results: Compared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting -/- mice. In the exposed WT group, STING was activated mainly in F4/80 + macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast-related factor RANKL in Sting -/- mice. The treatment of the STING inhibitor C-176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting -/- mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C-176 administration. In vitro, TRAP staining showed fewer positive cells and qRT-PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting -/- and C-176 treated BMMs., Conclusions: STING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C-176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis., (© 2024 British Endodontic Society. Published by John Wiley & Sons Ltd.)

For 3D animators, choreography with artificial intelligence has attracted more attention recently. However, most existing deep learning methods mainly rely on music for dance generation and lack sufficient control over generated dance motions. To address this issue, we introduce the idea of keyframe interpolation for music-driven dance generation and present a novel transition generation technique for choreography. Specifically, this technique synthesizes visually diverse and plausible dance motions by using normalizing flows to learn the probability distribution of dance motions conditioned on a piece of music and a sparse set of key poses. Thus, the generated dance motions respect both the input musical beats and the key poses. To achieve a robust transition of varying lengths between the key poses, we introduce a time embedding at each timestep as an additional condition. Extensive experiments show that our model generates more realistic, diverse, and beat-matching dance motions than the compared state-of-the-art methods, both qualitatively and quantitatively. Our experimental results demonstrate the superiority of the keyframe-based control for improving the diversity of the generated dance motions.

Background: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care., Methods: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed., Results: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities., Conclusion: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons., (© 2024. The Author(s).)

Color centers (CCs) in nanostructured diamond are promising for optically linked quantum technologies. Scaling to useful applications motivates architectures meeting the following criteria: C1 individual optical addressing of spin qubits; C2 frequency tuning of spin-dependent optical transitions; C3 coherent spin control; C4 active photon routing; C5 scalable manufacturability; and C6 low on-chip power dissipation for cryogenic operations. Here, we introduce an architecture that simultaneously achieves C1-C6. We realize piezoelectric strain control of diamond waveguide-coupled tin vacancy centers with ultralow power dissipation necessary. The DC response of our device allows emitter transition tuning by over 20 GHz, combined with low-power AC control. We show acoustic spin resonance of integrated tin vacancy spins and estimate single-phonon coupling rates over 1 kHz in the resolved sideband regime. Combined with high-speed optical routing, our work opens a path to scalable single-qubit control with optically mediated entangling gates.

Determining the optimal structures and clarifying the corresponding hierarchical evolution of transition metal clusters are of fundamental importance for their applications. The global optimization of clusters containing a large number of atoms, however, is a vastly challenging task encountered in many fields of physics and chemistry. In this work, a high-efficiency self-adaptive differential evolution with neighborhood search (SaNSDE) algorithm, which introduced an optimized cross-operation and an improved Basin Hopping module, was employed to search the lowest-energy structures of Co N , Pt N , and Fe N ( N = 3-200) clusters. The performance of the SaNSDE algorithm was first evaluated by comparing our results with the parallel results collected in the Cambridge Cluster Database (CCD). Subsequently, different analytical methods were introduced to investigate the structural and energetic properties of these clusters systematically, and special attention was paid to elucidating the structural evolution with cluster size by exploring their overall shape, atomic arrangement, structural similarity, and growth pattern. By comparison with those results listed in the CCD, 13 lower-energy structures of Fe N clusters were discovered. Moreover, our results reveal that the clusters of three metals had different magic numbers with superior stable structures, most of which possessed high symmetry. The structural evolution of Co, Pt, and Fe clusters could be, respectively, considered as predominantly closed-shell icosahedral, Marks decahedral, and disordered icosahedral-ring growth. Further, the formation of shell structures was discovered, and the clusters with hcp-, fcc-, and bcc-like configurations were ascertained. Nevertheless, the growth of the clusters was not simply atom-to-atom piling up on a given cluster despite gradual saturation of the coordination number toward its bulk limit. Our work identifies the general growth trends for such a wide region of cluster sizes, which would be unbearably expensive in first-principles calculations, and advances the development of global optimization algorithms for the structural prediction of clusters.

Introduction: The human leukocyte antigen (HLA) has been linked to the majority of autoimmune diseases (ADs). However, non-HLA genes may be risk factors for ADs. A number of genes encoding proteins involved in regulating T-cell and B-cell function have been identified as rheumatoid arthritis (RA) susceptibility genes., Methods: In this study, we investigated the association between RA and single-nucleotide polymorphisms (SNPs) of co-stimulatory or co-inhibitory molecules in 124 RA cases and 100 healthy controls without immune-related diseases [including tumor necrosis factor superfamily member 4 (TNFSF4), CD28, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and programmed cell death protein 1 (PDCD1)]., Results: The results showed that there were 13 SNPs associated with RA, including rs181758110 of TNFSF4 (CC vs. CT, p = 0.038); rs3181096 of CD28 (TT vs. CC + CT, p = 0.035; CC vs. TT, p = 0.047); rs11571315 (TT vs. CT, p = 0.045), rs733618 (CC vs. TT + CT, p = 0.043), rs4553808 (AA vs. AG vs. GG, p = 0.035), rs11571316 (GG vs. AG vs. AA, p = 0.048; GG vs. AG + AA, p = 0.026; GG vs. AG, p = 0.014), rs16840252 (CC vs. CT vs. TT, p = 0.007; CC vs. CT, p = 0.011), rs5742909 (CC vs. CT vs. TT, p = 0.040), and rs11571319 of CTLA4 (GG vs. AG vs. AA, p < 0.001; GG vs. AG + AA, p = 0.048; AA vs. GG + AG, p = 0.001; GG vs. AA, p = 0.008; GG vs. AG, p ≤ 0.001); and rs10204525 (TT vs. CT + CC, p = 0.024; TT vs. CT, p = 0.021), rs2227982 (AA vs. GG, p = 0.047), rs36084323 (TT vs. CT vs. CC, p = 0.022; TT vs. CT + CC, p = 0.013; CC vs. TT + CT, p = 0.048; TT vs. CC, p = 0.008), and rs5839828 of PDCD1 (DEL vs. DEL/G vs. GG, p = 0.014; DEL vs. DEL/G + GG, p = 0.014; GG vs. DEL + DEL/G, p = 0.025; DEL vs. GG, p = 0.007)., Discussion: Consequently, these SNPs may play an important role in immune regulation, and further research into the role of these SNPs of immune regulatory genes in the pathogenesis of RA is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Wen, Lin, Hsu and Yu.)

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves., Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined., Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger ( p  = 0.019), more commonly unvaccinated ( p  = 0.048) or exposed to infections ( p  < 0.001), and had higher rates of symptoms ( p  = 0.003) or shared living room ( p  < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p  < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p  < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p  = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p  = 0.018)., Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chai, Wu, Zhang, Wang, Yang, Shi, Wang, Zhang, Chen, Fan, Wen, Yang, Li, Liu, Zheng, Jiang, Qian, Tao, Qian, Wang, Chen, Xu and Wang.)

Nitrogen (N) deposition in the context of human activities continuously affects the carbon cycle of ecosystems. The effect of N deposition on soil organic carbon is related to the differential responses of different carbon fractions. To investigate the changes in soil organic carbon fraction and its influencing factors in the context of short-term N deposition, four N addition gradients:0 (CK), 1.5 (N1), 3 (N2), and 6 (N3) g·(m 2 ·a) -1 were set up in acacia plantations based on field N addition experiments, and the soil physicochemical properties, microbial biomass, and enzyme activities were measured in June and September. The results showed that:① exogenous N input reduced soil pH, promoted the increase in soluble organic carbon content, and increased soil nitrogen effectiveness. ② Short-term N addition significantly reduced soil organic carbon content, and the response of each component of organic carbon to N addition was different. Among them, the content of easily oxidized organic carbon was significantly reduced and reached the lowest value under the N2 treatment, with 54.4% and 48.2% reduction compared with that of the control, respectively, and the content of inert organic carbon increased, although the increase was not significant. Nitrogen addition reduced the soil carbon pool activity and improved the stability of the soil carbon pool. Soil carbon pool activity reached its lowest under the N3 and N2 treatments, with a decrease of 53.3% and 52.80%, respectively, compared to that of the control. ③Random forest modeling indicated that the soil microbial biomass stoichiometry ratio, microbial biomass carbon, and AP were the key factors driving the changes in soil organic carbon activity under short-term N addition, explaining 65.96% and 66.68% of the changes in oxidizable organic carbon and inert organic carbon, respectively. Structural equation modeling validated the results of the random forest modeling, and soil microbial biomass stoichiometric ratios significantly influenced carbon pool activity. Short-term nitrogen addition changed soil microbial biomass and its stoichiometric ratio in the acacia plantation forest mainly through two pathways, i.e., increasing soil nitrogen effectiveness and promoting soil acidification and inhibiting extracellular carbon hydrolase activity, thus changing the soil carbon fraction ratio and participating in the soil organic carbon cycling process.

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ 2 =36.01, P <0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ 2 =24.63, P <0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs . 53.4%, χ 2 =2.66, P =0.102). Older patients had worse OS ( HR =1.02, P =0.011) and EFS ( HR =1.01, P =0.027). Patients receiving adjuvant therapy had a lower risk of death ( HR =0.62, P =0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence ( HR =2.48, P =0.002) and a higher risk of death ( HR =2.03, P =0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.

The development of general methods for asymmetric benzylation of prochiral carbon nucleophiles remains a challenge in organic synthesis. The merging of ruthenium catalysis and N-heterocyclic carbene (NHC) catalysis for asymmetric redox benzylation of enals has been achieved, which opens up strategic opportunities for the asymmetric benzylation reactions. A wide range of 3,3'-disubstituted oxindoles with a stereogenic quaternary carbon center widely existing in natural products and biologically interesting molecules is successfully obtained with excellent enantioselectivities [up to 99% enantiomeric excess (ee)]. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of oxindole skeletons. Furthermore, the linear correlation between ee values of NHC precatalyst and the product elucidated the independent catalytic cycle of either the NHC catalyst or the ruthenium complex.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 ( Cdk5 ) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson's disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca 2+ -activated K + channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5 -deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre ; Cdk5 f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases., (Copyright © 2023 Chu Tong et al.)

A growing number of studies showed that single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA)-related genes were associated with the outcome of hematopoietic stem cell transplantation (HSCT). Thus, other SNPs located nearby the classical HLA genes must be considered in HSCT. We evaluated the clinical feasibility of MassARRAY by comparing to Sanger sequencing. The PCR amplicons with each one of the 17 loci that were related to the outcomes of HSCT published by our previous study were transferred onto a SpectroCHIP Array for genotyping by mass spectrometry. The sensitivity of MassARRAY was 97.9% (614/627) and the specificity was 100% (1281/1281), where the positive predictive value (PPV) was 100% (614/614) and the negative predictive value (NPV) was 99.0% (1281/1294). MassARRAY is high-throughput, which can accurately analyze multiple SNPs at the same time. Based on these properties, we proposed that it could be an efficient method to match the genotype between the graft and the recipient before transplantation., (© 2023. The Author(s).)

Background: Changes in ABO blood type caused by a gradual decrease in antigen expression have been found in patients with acute myeloid leukemia (AML). Studies have indicated that alteration of ABO gene methylation accounts for 50% of acquired weak ABO antigen expression in patients with leukemia. However, the molecular mechanisms contributing to the remaining 50% of cases are unknown. We hypothesize that deregulation of miRNA is correlated with weak ABO antigen expression in patients with AML., Methods: Blood samples of 19 patients with AML and 12 healthy controls were collected, in which the blood type was not changed in these AML patients. Flow cytometric analysis was applied to measure the ABO antigen expression titer among AML patients and controls. A total of 18 leukemia-related miRNAs were analyzed via quantitative real-time polymerase chain reactions., Results: We found that miRNA profiles were correlated with the AML patients, especially in those who had constant or weakened ABO antigen expressions. Compared with healthy controls, the miR-16 and miR-451 expression were significantly lower in either AML cases with weak ABO antigen expressions (p = 0.003, p = 0.028, respectively) or AML cases with constant ABO antigen expressions (p = 0.043, p = 0.040, respectively). Although not statistically significant, decreasing trends in the miR-451 and miR-16 expressions in the AML patients with weakened ABO were observed compared to those with constant ABO antigens. The weak ABO antigen expression might correlate with miRNAs, especially miR-16 and miR-451., Conclusion: This study indicated that decreasing in miR-16 and miR-451 was associated with AML and AML with weakened ABO expression. In the future, we will continue to include more cases and exclude the others factor influencing ABO antigen expression, promoter methylation and oxidative stress, to replicate the results of this study and investigate the underlying mechanism of decreasing miR-16 and miR-451 in AML patients with varied ABO antigen expression levels., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Purpose: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI)., Patients and Methods: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety., Results: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups., Conclusion: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

In a prior study, we discovered that hematopoietic stem cell transplantation (HSCT) and/or autoimmune diseases, such as systemic lupus erythematosus, were associated with the rs1234314 C/G and rs45454293 C/T polymorphisms of TNFSF4 , the rs5839828 C > del and rs36084323 C > T polymorphisms of PDCD1 , and the rs28541784C/T, rs200353921A/T, rs3181096C/T, and rs3181098 G/A polymorphisms of CD28 . However, the association does not imply causation. These single nucleotide polymorphisms (SNPs) are all located in the promoter region of these genes, so we used the dual-luminescence reporter assay to explore the effect of single nucleotide polymorphisms (SNPs) on transcriptional activity. For each promoter-reporter with a single SNP mutation, more than 10 independent experiments were carried out, and the difference in transcription activity was compared using one-way ANOVA and Tukey's honestly significant difference test. The results showed that the G-allele of rs1234314 had 0.32 ± 0.09 times the average amount of relative light units (RLU) compared to the C-allele ( p = 0.003), the T-allele of rs45454293 had 4.63 ± 0.92 times the average amount of RLU compared to the C-allele ( p < 0.001), the del-allele of rs5839828 had 1.37 ± 0.24 times the average amount of RLU compared to the G-allele ( p < 0.001), and the T-allele of rs36084323 had 0.68 ± 0.07 times the average amount of RLU compared to the C-allele ( p < 0.001). The CD28 SNPs studied here did not affect transcriptional activity. In conclusion, the findings of this study could only confirm that the SNP had a bio-functional effect on gene expression levels. According to the findings, several SNPs in the same gene have bio-functions that affect transcriptional activity. However, some increase transcriptional activity while others decrease it. Consequently, we inferred that the final protein level should be the integration result of the co-regulation of all the SNPs with the effect on transcriptional activity.

Spirooxindoles have emerged as promising architectures for engineering biologically active compounds. The diastereodivergent construction of unique scaffolds of this type with full control of continuous chiral centers including an all-carbon quaternary stereogenic center is yet to be developed. Here, we report an unprecedented diastereodivergent desymmetric [3 + 3] annulation of oxabicyclic alkenes with enals enabled by N-heterocyclic carbene (NHC)/Rh cooperative catalysis, leading to a series of enantiomerically enriched spirooxindole lactones with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >95:5 dr). The combined catalyst system comprises a rhodium complex that controls the configuration at the electrophilic carbon and an NHC catalyst that controls the configuration at the nucleophilic oxindole-containing carbon; thus, four stereoisomers of the spirooxindole products can be readily obtained simply by switching the configurations of the two chiral catalysts. Transformations of the chiral spirooxindoles delivered synthetically useful compounds. Importantly, those chiral spirooxindoles arrested mammalian cells in mitosis and exhibited potent antiproliferative activities against HeLa cells. Significantly, both absolute and relative configurations exert prominent effects on the bioactivities, underscoring great importance of catalytic asymmetric diastereodivergent synthesis beyond creating useful tools for the exploration of structure-activity relationships.

Cisplatin is a widely used standard chemotherapy for various cancers. However, cisplatin treatment is associated with severe ototoxicity. Fucoidan is a complex sulfated polysaccharide mainly derived from brown seaweeds, and it shows multiple bioactivities such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. Despite evidence of the antioxidant effects of fucoidan, research on its otoprotective effects remains limited. Therefore, the present study investigated the otoprotective effects of fucoidan in vitro using the mouse cochlear cell line UB/OC-2 to develop new strategies to attenuate cisplatin-induced ototoxicity. We quantified the cell membrane potential and analyzed regulators and cascade proteins in the apoptotic pathway. Mouse cochlear UB/OC-2 cells were pre-treated with fucoidan before cisplatin exposure. The effects on cochlear hair cell viability, mitochondrial function, and apoptosis-related proteins were determined via flow cytometry, Western blot analysis, and fluorescence staining. Fucoidan treatment reduced cisplatin-induced intracellular reactive oxygen species production, stabilized mitochondrial membrane potential, inhibited mitochondrial dysfunction, and successfully protected hair cells from apoptosis. Furthermore, fucoidan exerted antioxidant effects against oxidative stress by regulating the Nrf2 pathway. Therefore, we suggest that fucoidan may represent a potential therapeutic agent for developing a new otoprotective strategy.

Recent works have achieved remarkable performance for action recognition with human skeletal data by utilizing graph convolutional models. Existing models mainly focus on developing graph convolutional operations to encode structural properties of a skeletal graph, whose topology is manually predefined and fixed over all action samples. Some recent works further take sample-dependent relationships among joints into consideration. However, the complex relationships between arbitrary pairwise joints are difficult to learn and the temporal features between frames are not fully exploited by simply using traditional convolutions with small local kernels. In this paper, we propose a motif-based graph convolution method, which makes use of sample-dependent latent relations among non-physically connected joints to impose a high-order locality and assigns different semantic roles to physical neighbors of a joint to encode hierarchical structures. Furthermore, we propose a sparsity-promoting loss function to learn a sparse motif adjacency matrix for latent dependencies in non-physical connections. For extracting effective temporal information, we propose an efficient local temporal block. It adopts partial dense connections to reuse temporal features in local time windows, and enrich a variety of information flow by gradient combination. In addition, we introduce a non-local temporal block to capture global dependencies among frames. Our model can capture local and non-local relationships both spatially and temporally, by integrating the local and non-local temporal blocks into the sparse motif-based graph convolutional networks (SMotif-GCNs). Comprehensive experiments on four large-scale datasets show that our model outperforms the state-of-the-art methods. Our code is publicly available at https://github.com/wenyh1616/SAMotif-GCN.

Objective: To perform a cost-effectiveness analysis of endoscopic surgery versus intensity-modulated radiotherapy in the treatment of locally recurrent nasopharyngeal carcinoma (rNPC) from a health-economic perspective. Methods: From September 30, 2011 to January 16, 2017, a total of 200 patients were enrolled in the First Affiliated Hospital of Sun Yat-sen University, the First People's Hospital of Foshan, and Sun Yat-sen University Cancer Center. These patients were diagnosed as locally rT1-rT3 stage rNPC and were randomly assigned 1︰1 to the endoscopic surgery group (ENPG) and the intensity-modulated radiotherapy group (IMRT). There were 69 males and 31 females in ENPG, aging from 38 to 55 years. There were 72 males and 28 females in IMRT aging from 41 to 54 years. A retrospective cost-effectiveness analysis of the cohort was conducted using a Markov model. For each modality, data on survival and quality-adjusted life year (QALY) were sourced from relevant articles, and cost prices were included regarding treatment. Weibull distribution was used to estimate time-dependent transition probability. Beta-regression was used to convert the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to utility. Results: The total cost of ENPG was 29 611.88 yuan, and the total cost of IMRT was 110 082.51 yuan. The incremental cost-effectiveness ratio (ICER) of ENPG versus radiotherapy for locally rNPC was -85 555.88 yuan/QALY, which was less than 3 times of Chinese gross domestic product (GDP) per capita. Sensitivity analysis showed that the cost of IMRT had the greatest impact on ICER. ICER was stable within 10% fluctuation of all the parameters. Conclusion: It is economical cost-effective to treat locally rNPC with ENGP versus IMRT.

Recently, combining immunotherapy and chemotherapy has become a promising strategy to treat cancer. However, this therapeutic strategy still has its limitations because of the adverse effects caused by the simultaneous administration of multiple therapeutic agents. Using nanoparticles is an effective approach to successfully combine these therapies because they can reduce side effects, increase circulation time, and ensure the delivery of cytotoxic agents to tumor tissues. In this study, dual pH-sensitive and tumor microenvironment (TME)-active targeting micelles comprising poly(propyl methacrylate- co -glucosamine/histidine/doxorubicin) (P(PAA- co -GLU/HIS/DOX) and methoxy-poly(ethylene glycol)- block -poly(l-lysine) were prepared to encapsulate an immunomodulator, imiquimod (IMQ). Because these micelles can expose glucose targeting ligands at the TME and pH-dependently release IMQ and DOX, micelles effectively inhibit the growth of 4T1 cells selectively and highly accumulate in 4T1 cells as the pH decreased to 6.5. Moreover, in RAW 264.7 ​cells, these micelles prevent cell death and induce M1 macrophage polarization. In 4T1 orthotopic tumor-bearing mice, micelles not only exhibited high tumor accumulation, effective tumor inhibition, and fewer adverse effects, but also dramatically increased the number of mature dendritic cells, activate cytotoxic T cells, and polarize M1-like macrophages in tumor tissues. Overall, these micelles exhibit precise pH responsiveness and ideal drug delivery capabilities for combined chemo- and immunotherapy; these results significantly contribute to the future development of nanomedicines in cancer therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

People often worry about the side effects after vaccination, reducing the willingness to vaccinate. Thus, we tried to find out the risk of single nucleotide polymorphism (SNP) vaccines to improve the willingness and confidence in vaccination. Allergic and inflammatory reactions are the common vaccine side effects caused by immune system overreaction. In addition, a previous study showed significantly higher frequency of febrile reactions to measles vaccines in American Indians than in Caucasian children, indicating that the side effects varied in accordance with genetic polymorphisms in individuals. Thus, SNPs of immune regulatory genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4) and programmed cell death protein 1 (PDCD1) were included in this study to analyze their association with vaccine side effects. Moreover, 61 healthy participants were asked on the number of doses they received, the brand of the vaccine, and the side effects they suffered. We found that several SNPs were associated with side effects after the first or second dose of mRNA or adenoviral vector vaccines. Furthermore, these SNPs were associated with several autoimmune diseases and cancer types; thus, they played an important role in immune regulation. Moreover, rs3181096 and rs3181098 of CD28, rs733618 and rs3087243 of CTLA, and rs1234314 of TNFSF4 were associated with mild vaccine side effects induced by mRNA and adenoviral vector vaccines, which would play a potential role in vaccine-induced immune responses and may further lead to fatal side effects. These results could serve as a basis for investigating the mechanism of vaccine side effects. Furthermore, it was hoped that these results would address public concerns about the side effects of the COVID-19 vaccination. In clinical application, a rapid screening test can be performed to assess the risk of vaccine side effects before vaccination and provide immediate treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wen, Lin and Hsu.)

Nanoalloys have attracted extensive interest from the research and industrial community due to their unique properties. In this work, the thermally activated microstructural evolution and resultant collapse of PtIrCu nanorings were investigated using molecular dynamics simulations. Three PtIrCu nanorings with a fixed outer radius and varied inner radii were addressed to investigate the size effects on their thermal and shape stabilities. The shape factor was introduced to monitor their shape changes, and a common neighbor analysis was employed to characterize the local structures of atoms. The results reveal that both the thermal and shape stabilities of these nanorings can be remarkably improved by decreasing the inner radius. Furthermore, they all experienced the evolutionary process from ring to pie and spherelike morphologies, finally resulting in structural collapse. The stacking faults were observed in these rings during the heating process. Our work sheds light on the fundamental understanding of alloyed nanorings subjected to heating, hence offering a theoretical foundation for their syntheses and applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Purpose: The aim of this study was to retrospectively evaluate the oncologic outcomes of sinonasal malignancies (SNMs) of various histologic subtypes and investigate the impact of multimodality treatment on prognosis of SNM., Methods: SNM patients treated with curative-intent surgery from 2000 to 2018 were included. The primary outcomes were overall survival (OS). Survival was then assessed through Cox proportional hazards models., Results: Three hundred and three patients were eligible for the analysis. The 5-year OS and event-free survival (EFS) were 61.0% (95% CI: 55.4%-67.1%) and 46.2% (95% CI: 40.4%-52.7%). The 5-year OS was the worst for malignant melanoma and the best for adenocarcinoma. Patients who received surgery had better OS than those who only received radiotherapy and/or chemotherapy. Endoscopic surgery had better OS than the open approach ( p < 0.05). Microscopically margin-negative resection (R0 resection) significantly benefited OS and EFS ( p < 0.001). No significant difference in OS was observed between patients who received macroscopic complete resection (R1 resection) followed by adjuvant therapy and patients who received R0 resection. Older age (HR = 1.02, p = 0.02), R1 resection (HR = 1.99, p = 0.02), sinonasal surgical history of more than 3 months before diagnosis (HR = 2.77, p = 0.007), and radiotherapy history (HR = 3, p = 0.006) are risk factors for worse EFS., Conclusions: Curative-intent surgery is irreplaceable in the treatment of SNM. The endoscopic approach is an effective alternative to the open approach. EFS is worse among patients with older age, R1 resection, sinonasal surgical history of more than 3 months before diagnosis, and radiotherapy history., Competing Interests: All authors have completed the ICMJE uniform disclosure form. Y-HW reports that he is funded by the National Natural Science Foundation of China (NSFC) grants (81900918). W-PW reported that he was funded by the National Natural Science Foundation of China (NSFC) grants (82020108009 and 81870696), Guangdong Natural Science Foundation of China grants (2018B030312008), Guangdong Research Program of Key Fields in Province (2020B1111300003), and the Key-Area Research and Development of Guangdong Province (2020B1111190001). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wen, Wei, Chen, Huang, Lu, Zheng, Li, Wen and Wen.)

Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade., Materials and Methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors., Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers., Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SW declared a shared affiliation with the authors to the handling editor at time of review., (Copyright © 2022 Hu, Sun, Wen, Ma, Chen, Chen, Lei and Wen.)

A crystal phase is a key factor to determine the physical and chemical properties of crystalline materials. As a new class of nanoscale structures, heterophase nanoparticles, which assemble conventional and unconventional phases, exhibit exceptional properties in comparison with their single-phase counterparts. In this work, we explored the thermodynamic stability of Au, Co, and AuCo heterophase nanoparticles with fcc and hcp phases by using molecular dynamics simulations. These heterostructured nanoparticles were continuously heated to examine their thermally activated structural evolutions. Au and Co single-phase nanoparticles were also considered for comparison. The results show that the phase transition between fcc and hcp is absent in these heterophase nanoparticles despite the existence of an unconventional phase. Although the melting of Au and Co heterophase nanoparticles is homogeneous, AuCo heterophase nanoparticles show heterogeneous melting, i.e. , the Au fcc domain firstly melts, followed by the melting of the Co hcp domain, exhibiting a typical two-stage melting characteristic and resulting in the existence of a solid-core/liquid-shell structure within a considerable temperature region. Furthermore, the mutual diffusion of atoms between fcc and hcp domains is observed in the Au and Co heterophase nanoparticles. However, the unidirectional diffusion from the Au domain to the Co domain is found in the AuCo heterophase nanoparticles prior to their overall melting. This study deepens the fundamental understanding of the thermodynamic evolution of metallic heterogeneous nanoparticles and provides mechanistic and quantitative guidance for the rational design and applications of nanoscale multiphase heterostructures.

Platelet concentrates (PCs) are widely used in regenerative medicine; as it is produced from freeze-thawing PC, platelet lysate (PL) has a longer shelf life. The thrombotic risk of PL therapy needs to be explored since PL and PC contain cytokines that contribute to platelet aggregation and thrombus formation. Whole blood samples of 20 healthy subjects were collected; PL was produced from PCs with expired shelf life through freeze-thawing. The direct mixing of PL with platelet-rich plasma (PRP) or whole blood was performed. In addition, rotational thromboelastometry (ROTEM) was used to investigate whether PL enhanced coagulation in vitro; the effects of fibrinogen depletion and anticoagulants were evaluated to prevent hypercoagulation. The results showed that PL induced platelet aggregation in both PRP and whole blood. In ROTEM assays, PL was shown to cause a significantly lower clotting onset time (COT) and clot formation time (CFT), and a significantly greater α angle and maximum clot firmness (MCF). Compared with the controls, which were 1:1 mixtures of normal saline and whole blood, fibrinogen depletion of PL showed no significant difference in CFT, α angle and MCF. Moreover, heparin- and rivaroxaban-added PL groups demonstrated no clot formation in ROTEM assays. Platelet lysate-induced hypercoagulability was demonstrated in vitro in the present study, which could be prevented by fibrinogen depletion or the addition of an anticoagulant.

The diruthenium-based linear mixed valence complex trans -[Ru 2 (ap) 4 -NC-Ru(DMAP) 4 -CN-Ru 2 (ap) 4 ][PF 6 ] 2 (12+[PF6]2) (ap = 2-anilinopyridinate, DMAP = 4-dimethylaminopyridine) and its two-electron oxidation product 14+[PF6]4 have been synthesized and fully characterized. The investigation reveals that complex 12+ displays a single MMCT transition, whereas complex 14+ has three identified MMCT transitions (MMCT-1, MMCT-2 and MMCT-3) upon oxidation. Interestingly, MMCT-2 in complex 14+ might result from the transition from the Ru III -NC-Ru II -CN-Ru III component, which is composed of the central Ru II and its two neighboring Ru III atoms from the cluster RuVI2 units, to both the terminal Ru III atoms of the same cluster RuVI2 units, which is supported by the TDDFT calculations.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Global optimization of multicomponent cluster structures is considerably time-consuming due to the existence of a vast number of isomers. In this work, we proposed an improved self-adaptive differential evolution with the neighborhood search (SaNSDE) algorithm and applied it to the global optimization of bimetallic cluster structures. The cross operation was optimized, and an improved basin hopping module was introduced to enhance the searching efficiency of SaNSDE optimization. Taking (PtNi) N ( N = 38 or 55) bimetallic clusters as examples, their structures were predicted by using this algorithm. The traditional SaNSDE algorithm was carried out for comparison with the improved SaNSDE algorithm. For all the optimized clusters, the excess energy and the second difference of the energy were calculated to examine their relative stabilities. Meanwhile, the bond order parameters were adopted to quantitatively characterize the cluster structures. The results reveal that the improved SaNSDE algorithm possessed significantly higher searching capability and faster convergence speed than the traditional SaNSDE algorithm. Furthermore, the lowest-energy configurations of (PtNi) 38 clusters could be classified as the truncated octahedral and disordered structures. In contrast, all the optimal (PtNi) 55 clusters were approximately icosahedral. Our work fully demonstrates the high efficiency of the improved algorithm and advances the development of global optimization algorithms and the structural prediction of multicomponent clusters.

Gentamicin is an important aminoglycoside antibiotic used in the treatment of gram‑negative bacterial infections, but nephrotoxicity and ototoxicity reduce its utility. The autophagy pathway is involved in damage of auditory hair cells. With the aim of developing new strategies for attenuating gentamicin ototoxicity, the present study investigated the otoprotective mechanism of 2,3,4',5‑tetrahydroxystilbene‑2‑O‑β‑D-glucoside (THSG) in vitro using the mouse cochlear cell line UB/OC‑2. MTT assay demonstrated that gentamicin reduced UB/OC‑2 cell viability and western blotting showed that gentamicin upregulated autophagy‑related proteins, such as Beclin, autophagy related 5 and LC3‑II. THSG significantly attenuated gentamicin‑induced cytotoxicity, clearly reduced LDH release observed by LDH assay and decreased the expression of autophagy‑related proteins. Reverse‑transcription‑quantitative (RT‑q) PCR and western blotting showed that THSG against gentamicin‑induced autophagy via suppressing the expression of Sesn2, at both the mRNA and protein level and a possible involvement of AMP‑activated protein kinase (AMPK)/mTOR signaling response. Collectively, the present study demonstrated that THSG decreased gentamicin‑induced ototoxicity in UB/OC‑2 cochlear cells via the autophagic signaling in regulating Sesn2/AMPK/mTOR pathway. These results suggested that THSG might be a new therapeutic agent with the potential to attenuate gentamicin ototoxicity.

Background: Taxifolin is a flavanonol with efficacious cytoprotective properties, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, and nephroprotective effects. However, the potential protective effects of taxifolin against gentamicin-induced ototoxicity have not been confirmed. In this study, the possible mechanisms underlying the effects of taxifolin on gentamicin-induced death of UB/OC-2 cochlear cells were investigated., Methods: Mouse cochlear UB/OC-2 cells with or without taxifolin pretreatment were exposed to gentamicin, and the effects on cytotoxicity, reactive oxygen species (ROS) production, mitochondrial permeability transition, and apoptotic marker expression were examined using biochemical techniques, flow cytometry, western blotting, and fluorescent staining., Results: Little or no apparent effect of taxifolin on cell viability was observed at concentrations less than 40 μM. Further investigations showed that gentamicin significantly inhibited cell viability in a concentration-dependent manner. Pretreatment with taxifolin attenuated gentamicin-induced lactate dehydrogenase release, as well as cellular cytotoxicity. In addition, taxifolin significantly prevented gentamicin-induced cell damage by decreasing ROS production, stabilizing mitochondrial membrane potential, and downregulating the mitochondrial pathway of apoptosis., Conclusion: In summary, pretreatment with taxifolin is effective for mitigating gentamicin-induced apoptotic cell death mediated by the mitochondrial pathway. Our data suggest that taxifolin provides a new approach to combat gentamicin-induced ototoxicity., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)