Search

Summary: Age-related functional impairments (ARFIs) contribute to the loss of independence in older adults, but their progressions, interrelations, and combined relations with mortality are largely unknown. We conducted a prospective study among 17,914 participants in the Health and Retirement Study (2000–2020). The incidence rates of visual impairment, hearing impairment, physical frailty, and cognitive impairment increased exponentially with age, while those of restless sleep and depression increased relatively slowly. These ARFIs were associated with each other in temporal sequence and constituted a hazard network. We observed a dose-response relationship between the number of ARFIs and mortality risk, and the dyads involving physical frailty demonstrated the strongest associations with mortality. Our findings may assist in the identification of individuals at higher mortality risk and highlight the potential for future investigations to explore the impact of multiple ARFIs in aging.

IntroductionSeagrasses play a key role in biodiversity maintenance, sediment stabilization, and carbon reduction. Due to the significant decline of seagrass populations worldwide, many projects to restore seagrass by transplantation have been undertaken in recent decades. However, effective restoration technologies required to rapidly restore seagrass on Hainan Island are yet to be developed.MethodsIn this study, an experiment was carried out to investigate methods for alleviating continuous degradation of seagrass beds on Hainan Island. Seagrass were transplanted by “single-plant-fixed-distance transplantation” method, survival rate, shoot formation rate, coverage and shoot density of transplanting plants were monitored for 23 months.ResultsOver 67% of T. hemprichii and 90% of E. acoroides were still alive, shoot density were over 11 shoots/m2 and 15 shoots/m2 respectively after almost two years, E. acoroides was more likely to survive than T. hemprichii both in Gaolong Bay and Xincun lagoon. Because of the damage to below-ground tissues, the survival rate, shoot formation rate, coverage and shoot density decreased during the first one year after transplantation, then increased gradually.DiscussionWe considered transplantation established successfully of T. hemprichii and E. acoroides in the new site was about 12 months. In addition, T. hemprichii was suitable for transplanted in Xincun lagoon, and E. acoroides was suitable for transplanted in Gaolong bay. The results demonstrated that the growth of transplanted seagrass was greatly affected by suspend solids and DIN. The results of this study may provide data support and scientific basis for seagrass transplantation in South China.

BackgroundThe hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT.MethodsAcute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24 h of MT. Clinical outcomes after 3 months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS > 2) at 3 months, while the secondary outcome was death within 3 months.ResultsA total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24 h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24 h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520–0.803, p

In this study, a rice starch–nobiletin (NOB) complex with well digestion-resistance by in-situ extrusion was chosen as a supplementary diet to protect against ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. After oral administration, the complex alleviated colon damage caused by DSS, decreased serum levels of proinflammatory cytokines and colon oxidative stress, and improved the expression of tight junction proteins. Meanwhile, the complex may modify the gut microbiota by increasing its diversity and promoting potentially beneficial bacteria, as well as boosting short-chain fatty acid levels. Correlation analysis further revealed that proinflammatory cytokines and other injury factors were negatively related to Firmicutes and Verrucomicrobiota (phylum level), as well as Lactobacillus and Akkermansia (genus level). Overall, our results show that the rice starch–NOB complex protects intestinal barrier dysfunction in UC and may be a healthy addition to rice starch diets.

Summary: Drought can adversely influence the crop growth and production. Accordingly, sunflowers have strong adaptability to drought; hence, we conducted analyses for sunflower seedlings with drought stress and rehydration drought acclimation through physiological measurements and transcriptomics. It showed that drought can cause the accumulation of ROS and enhance the activity of antioxidant enzymes and the content of osmolytes. After rehydration, the contents of ROS and MDA were significantly reduced concomitant with increased antioxidant activity and osmotic adjustment. Totally, 2,589 DEGs were identified among treatments. Functional enrichment analysis showed that DEGs were mainly involved in plant hormone signal transduction, MAPK signaling, and biosynthesis of secondary metabolites. Comparison between differentially spliced genes and DEGs indicated that bHLH025, NAC53, and SINAT3 may be pivotal genes involved in sunflower drought resistance. Our results not only highlight the underlying mechanism of drought stress and rehydration in sunflower but also provide a theoretical basis for crop genetic breeding.

The development of efficient, low-cost, and environmentally friendly catalysts has the potential to significantly enhance the persulfate-based advanced oxidation technology for wastewater treatment. In this study, chitosan gel was ultilized as the biomass to be pyrolyzed by two-step pyrolysis method at 600 °C and 800 °C to produce biochar (BC-800). Results from the SEM, TEM, BET, Raman, and XPS characterizations showed that the BC-800 had a surface area of 1748 m2/g and a hierarchical pore structure with co-existing macropores, mesopores, and micropores, as well as an obvious graphitic carbon, pyridinic N, and graphitic N configurations. The prepared biochar was found to activate persulfate (PS) for rapid degradation of 2,4-dichlorophenol, with 90% of pollutants removed in 5 min due to the excellent mass transfer facilitated by the abundant pores. Chemical quenching experiments, EPR detection, and electrochemical analysis indicated that the degradation process was triggered by a nonradical pathway, in which the biochar acted as an electron transfer shuttle between the oxidant and pollutant. This electron transfer mechanism not only enabled the degradation system have a wide pH range for application, but it also demonstrated high resistance to inorganic anions in the aquatic environment. This research is expected to enhance the preparation method of hierarchical porous biochar and provide effective technical support for the biochar-activated PS for water purification.

Background and aims: Wnt signaling is essential for the maintenance of cancer stem cells (CSCs), but mutations in the β-catenin and APC genes are less common in non-small cell lung carcinoma (NSCLC). Thus, the mechanism underlying the constitutive activation of Wnt signaling in lung CSCs is still unknown. Materials and methods: Gene set enrichment analysis and immunohistochemistry were performed to establish the correlation between KDM6A/KM2B and CSC stemness. Human NSCLC cell lines were genetically manipulated for functional studies. Sphere formation assay and stemness gene expression profiling were examined to investigate the role of KDM6A/KMT2B in lung CSCs. Tumor xenograft assay were used to identify the function of KDM6A/KMT2B on tumorigenicity and tumor recurrence in vivo. Western blot analysis, coimmunoprecipitation and chromatin immunoprecipitation were performed to understand KDM6A/KMT2B mediated epigenetic regulation of Histone 3 lysine 4 methylation (H3K4me) on Wnt signaling pathway. Results: We discovered that the expression of Histone demethylase KDM6A and methyltransferase KMT2B correlate with the stemness of CSCs in NSCLC. KDM6A coordinates with KMT2B to activate the Wnt/β-catenin signaling pathway by regulating the H3K4me3 level and promotes the tumorigenicity and maintenance of CSC stemness. Furthermore, KDM6A/ KMT2B overexpression promotes the CSC chemoresistance and tumor recurrence both in vitro and in vivo. Inhibition of KDM6A and KMT2B potently suppress tumor initiation and recurrence in xenografted animal models. Conclusion: Our findings suggest that KDM6A and KMT2B mediate the constitutive activation of Wnt/β-catenin signaling in lung CSCs, potentially providing a therapeutic target for NSCLC.

Abstract In this study, we treated infected ankle bone defects with the induced membrane two-stage technique. The ankle was fused with a retrograde intramedullary nail in the second stage, and the aim of this study was to observe the clinical effect. We retrospectively enrolled patients with infected bone defects of the ankle admitted to our hospital between July 2016 and July 2018. In the first stage, the ankle was temporarily stabilized with a locking plate, and antibiotic bone cement was used to fill the defects after debridement. In the second stage, the plate and cement were removed, the ankle was stabilized with a retrograde nail, and tibiotalar-calcaneal fusion was performed. Then, autologous bone was used to rebuild the defects. The infection control rate, fusion success rate and complications were observed. Fifteen patients were enrolled in the study with an average follow-up of 30 months. Among them, there were 11 males and 4 females. The average bone defect length after debridement was 5.3 cm (2.1–8.7 cm). Finally, 13 patients (86.6%) achieved bone union without recurrence of infection, and 2 patients experienced recurrence after bone grafting. The average ankle-hindfoot function score (AOFAS) increased from 29.75 ± 4.37 to 81.06 ± 4.72 at the last follow-up. The induced membrane technique combined with a retrograde intramedullary nail for the treatment of infected bone defects of the ankle after thorough debridement is an effective treatment method.

Abstract Background The unique intracranial tumor microenvironment (TME) contributes to the immunotherapy failure for glioblastoma (GBM), thus new functional protein targets are urgently needed. Alternative splicing is a widespread regulatory mechanism by which individual gene can express variant proteins with distinct functions. Moreover, proteins located in the cell plasma membrane facilitate targeted therapies. This study sought to obtain functional membrane protein isoforms from GBM TME. Methods With combined single-cell RNA-seq and bulk RNA-seq analyses, novel candidate membrane proteins generated by prognostic splicing events were screened within GBM TME. The short isoform of MS4A7 (MS4A7-s) was selected for evaluation by RT-PCR and western blotting in clinical specimens. Its clinical relevance was evaluated in a GBM patient cohort. The function of MS4A7-s was identified by in vitro and in vivo experiments. MS4A7-s overexpression introduced transcriptome changes were analyzed to explore the potential molecular mechanism. Results The main expression product, isoform MS4A7-s, generated by exon skipping, is an M2-specific plasma membrane protein playing a pro-oncogenic role in GBM TME. Higher expression of MS4A7-s correlates with poor prognosis in a GBM cohort. In vitro cell co-culture experiments, intracranial co-injection tumorigenesis assay, and RNA-seq suggest MS4A7-s promotes activation of glioma-associated macrophages’ (GAMs) PI3K/AKT/GSK3β pathway, leading to M2 polarization, and drives malignant progression of GBM. Conclusions MS4A7-s, a novel splicing isoform of MS4A7 located on the surface of GAMs in GBM TME, is a predictor of patient outcome, which contributes to M2 polarization and the malignant phenotype of GBM. Targeting MS4A7-s may constitute a promising treatment for GBM.

Abstract Background Cytokine-induced memory-like natural killer (CIML NK) cells have been found to possess potent antitumor responses and induce complete remissions in patients with leukemia. However, the poor infiltration of transferred NK cells is a major obstacle in developing adoptive cell immunotherapy for solid tumors. In our study, we explored the potential of using the tumor-penetrating peptide iRGD to deliver activated CIML NK cells deep into tumor tissues. Methods After being briefly stimulated with interleukin-12 (IL-12), IL-15, and IL-18, CIML NK cells were assessed for their phenotype and function with flow cytometry. The penetrating and killing capability of iRGD-modified CIML NK cells in tumor spheroids was revealed by confocal microscopy. The anti-tumor efficacy of these modified CIML NK cells was tested in hepatocellular carcinoma (HCC) xenograft mouse models. Results Treating NK cells with cytokines led to a substantial activation, which was evidenced by the upregulation of CD25 and CD137. After a resting period of six days, CIML NK cells were still able to display strong activation when targeting HepG2 and SK-Hep-1 HCC cell lines. Additionally, CIML NK cells produced increased amounts of cytokines (interferon-gamma and tumor necrosis factor alpha) and exhibited heightened cytotoxicity towards HCC cell lines. The iRGD modification enabled CIML NK cells to infiltrate multicellular spheroids (MCSs) and, consequently, to induce cytotoxicity against the target cancer cells. Moreover, the CIML NK cells modified with iRGD significantly decreased tumor growth in a HCC xenograft mouse model. Conclusion Our findings demonstrate that CIML NK cells possess augmented potency and durability against HCC cell lines in vitro. Additionally, we have seen that the incorporation of iRGD to CIML NK cells facilitates enhanced infiltration and targeted destruction of MCSs. Moreover, the application of iRGD-modified CIML NK cells reveal remarkable anti-tumor efficacy against HCC in vivo.

Abstract Background To evaluate the diagnostic performance of radiologists on breast cancer with or without artificial intelligence (AI) support. Methods A retrospective study was performed. In total, 643 mammograms (average age: 54 years; female: 100%; cancer: 62.05%) were randomly allocated into two groups. Seventy‐five percent of mammograms in each group were randomly selected for assessment by two independent radiologists, and the rest were read once. Half of the 71 radiologists could read mammograms with AI support, and the other half could not. Sensitivity, specificity, Youden's index, agreement rate, Kappa value, the area under the receiver operating characteristic curve (AUC) and the reading time of radiologists in each group were analyzed. Results The average AUC was higher if the AI support system was used (unaided: 0.84; with AI support: 0.91; p

The noticeable difference in the coefficient of thermal expansion (CTE) for polytetrafluoroethylene (PTFE) coatings and copper substrates is a major challenge for thermal debonding of the copper-clad laminate (CCL) in high-frequency communications. Theoretically, ceramic fillers with low CTEs in the coating can effectively reduce the gap, and there remains a trade-off between the dispersibility of fillers and the interfacial interactions with the polymeric matrix. Here, we propose a novel approach to prepare a pentafluorobenzoyl chloride (PFBC)-modified polydopamine (PDA) shell on silica particles by using amidation. Such modified particles perform excellent dispersion and exhibit diminished interfacial gaps in the PTFE matrix, which highly reduces CTE to 77 ppm/°C, accounting for only 48.1% of the neat coating. Moreover, the composite exhibits enhanced mechanical strength and toughness, and consequently suppresses thermal debonding in CCL under high-temperature conditions. Therefore, results present a promising potential for its use in the next-generation CCL of high-frequency communication devices.

The mitochondrial antiviral-signaling protein (MAVS), a core adaptor protein in the retinoic-acid-inducible gene-I-like receptors (RLRs)-MAVS pathway, has been demonstrated to play an important role in antiviral immune response and tumor immunology. Previous studies revealed that ubiquitylation is a key mechanism in the regulation of the RLRs-MAVS axis and immune response. Multiple E3 ubiquitin ligases and deubiquitinating enzymes control MAVS ubiquitylation and changes in MAVS function. In this review, we summarize the biological function of ubiquitylation in MAVS-related signaling and provide new insight into immunotherapy approaches that target MAVS.

Global climate change, human activities, and environmental pollution impact coral reefs worldwide. The South China Sea coral reefs have been severely degraded. Genetic diversity among populations of coral is important to implement appropriate protection and restoration measures. Platygyra daedalea, widely distributed in the South China Sea, is stress-resistant and forms a dominant species in some regions. Analyzing the genetic diversity of P. daedalea may provide clues to enhance the resistance of reef-building corals. In this study, we employed one nuclear DNA fragment (ITS) and sixteen microsatellite loci to investigate the genetic diversity of coral host and high-throughput sequencing to investigate on the Symbiodiniaceae types in P. daedalea. (1) The populations of P. daedalea and Symbiodiniaceae types in P. daedalea on Hainan and Xisha Islands were divided into three groups: northern to western Hainan Island, eastern to southern Hainan Island, and Xisha Islands. The ribotypes distribution of coral hosts and the Symbiodiniaceae community composition were strongly correlated with environmental factors in the three areas, especially phosphate concentration and diffuse attenuation. (2) Environmental heterogeneity significantly affected the genetic diversity of coral hosts and diversity of Symbiodiniaceae types, especially nutrient concentration, which significantly affected the diversity of coral-algal symbiosis of P.daedalea even if the seawater nutrient content was within the normal range of coral life. (3) Coral hosts with different genotypes may prefer different Symbiodiniaceae types. This study provides new insights into the changes in the genetic structure and diversity of reef-building corals in the Indo-Pacific region.

Urticaria is a common skin condition encountered across various specialties in medicine, especially in dermatology and allergy/immunology practice. It has a heterogeneous presentation hence it is unsurprising that many skin conditions may be confused with urticaria. Urticaria may present as acute or chronic urticaria, the latter can be further categorised into chronic spontaneous and chronic inducible. In this article, we explore, explain, and summarise various skin lesions that are considered mimickers of urticaria, to promote understanding of each of the conditions highlighted, improve recognition, and reduce misdiagnosis.

ObjectivesRecent clinical studies have demonstrated that immunotherapy-based neoadjuvant therapy have promising effectiveness for patients with resectable non-small cell lung cancer (NSCLC) in terms of pathologic response. Therefore, we performed this study to investigate whether immunotherapy-based neoadjuvant therapy is effective and safe for patients with resectable NSCLC.Materials and methodsThis open-label observational two-arm clinical study was performed at Shanghai Chest Hospital in China with patients who had resectable NSCLC and received two to three cycles of immunotherapy-based neoadjuvant therapy or neoadjuvant chemotherapy alone, followed by surgical resection. The primary endpoint was a major pathologic response (MPR). The secondary endpoints include a complete pathological response (pCR), a radiologic response to neoadjuvant therapy (TRR), event-free survival (EFS), and overall survival (OS).ResultsA total of 51 patients was included in this clinical study, of which 31 patients received immunotherapy-based neoadjuvant therapy and 20 patients received neoadjuvant chemotherapy alone. The percentage of patients achieving a major pathologic response was 41.9% with immunotherapy-based neoadjuvant therapy and 15.0% (95% CI, 0.008 to 0.468; P = 0.043) with neoadjuvant chemotherapy alone. The percentage of patients with pathologic complete response was 19.4% in the immunotherapy-based group and 5% (95% CI, -0.069 to 0.318; P = 0.223) in the chemotherapy group. The radiographic response rate was 71% after immunotherapy-based neoadjuvant therapy and 60% (95% CI, -0.143 to 0.359; P = 0.417) after neoadjuvant chemotherapy. At a median follow-up of 28 months, the median EFS and OS endpoints were not reached.ConclusionsNeoadjuvant immunotherapy offers a considerable advantage over chemotherapy alone for resectable NSCLC in terms of the major pathologic response. Moreover, it did not enhance the risk of adverse events or hinder surgical resection.

Although the internal electric field (IEF) of bismuth oxyiodide (BiOI) is acknowledged as a potent driving force for efficient charge separation, enhancing the intensity of IEF remains a challenge. Herein, highly crystalline BiOI nanosheets with I‐rich surface are employed to intensify IEF and direct the charge migration. In comparison to I‐poor BiOI nanosheets, which possess Bi−O layer termination and I‐defects, the I‐rich BiOI demonstrates 62.5‐fold improvement in IEF intensity to its well‐developed high crystalline structure, and its IEF direction is reversed by the surface I‐rich layers. This intensified IEF of I‐rich BiOI induces numerous holes (h+) to migrate to the surface of primary exposed (001) facets and electrons (e−) to the lateral facets efficiently, resulting in efficient charge separation spatially. Additionally, the surface accumulates h+ and superoxide radicals and acts in synergy to enhance the photodegradation of phenol. The photocatalytic activity of the I‐rich BiOI is found to be approximately fivefold and threefold higher than that of I‐poor BiOI under full spectra and visible light, respectively. Herein, the manipulation of IEF through surface and bulk structure regulation of BiOI for efficient charge separation is discussed, expecting to rationally improve photocatalytic performances.

Summary: Invadopodia, being actin-rich membrane protrusions, play a vital role in tumor cell invasion and metastasis. Our previous studies have revealed some functions of the DOC-2/DAB2 interacting protein (DAB2IP) as a tumor suppressor. Nevertheless, the specific role and mechanism of DAB2IP in invadopodia formation remain unclear. Here, we find that DAB2IP effectively suppresses invadopodia formation and metastasis in breast cancer, both in vitro and in vivo. Additionally, DAB2IP could downregulate anaplastic lymphoma kinase (ALK), resulting in the inhibition of tyrosine phosphorylation of Cortactin and the prevention of invadopodia formation. DAB2IP competitively antagonizes the interaction between the deubiquitinating enzyme Ubiquitin-specific peptidase 10 (USP10) and ALK, leading to a decrease in the abundance of ALK protein. In summary, DAB2IP impairs the stability of ALK through USP10-dependent deubiquitination, suppressing Cortactin phosphorylation, thereby inhibiting invadopodia formation and metastasis of breast cancer cells. Furthermore, this study suggests a potential therapeutic strategy for breast cancer treatment.

Objective To explore the application effect of traditional teaching combined with problem based learning (PBL) in the teaching of transfusion medicine taking the chapter of Human Leukocyte Antigen System and Testing in Clinical Blood Transfusion Testing Technique as an example. Methods Firstly, practical problems in chapter Human Leukocyte Antigen System and Testing were analyzed. Then, in response to the key and difficult points in the teaching of this chapter, examples were given to illustrate the practical application of traditional teaching combined with PBL in the teaching of Clinical Blood Transfusion Testing Technique from the aspects of teaching objectives, teaching processes, course implementation and implementation effects. The teaching effectiveness was evaluated through a questionnaire. Results Traditional teaching combined with PBL helped students grasp important knowledge and techniques, break down thinking barriers, grasp internal connections and characteristics, simplify the learning process, stimulate interest in learning and enhance team collaboration. Meanwhile, students' exploration and innovation abilities could be further cultivated through extracurricular expansion by teachers, thus achieving ideal teaching effect. The questionnaire showed that over 90% of the students consider that combining traditional teaching with PBL was beneficial for improving teaching effect. Conclusion In the teaching of transfusion medicine, adopting traditional teaching combined with PBL according to the textbook content can improve the teaching effect, which is beneficial for the cultivation of comprehensive talents.

IntroductionPaeonia ostii T. Hong & J.X. Zhang (s.s.) (Chinese name, Fengdan) is a widely cultivated food-medicine plant in China, in which root bark, seed kernels, and flowers are utilized for their medicinal and edible values. However, other parts of the plant are not used efficiently, in part due to a poor understanding of their chemical composition and potential biological activity.MethodsUntargeted ultra-performance liquid chromatography–quadrupole time of flight–mass spectrometry (UPLC-Q-TOF-MS) metabolomics was applied to characterize the metabolic profiles of 10 different parts of P. ostii.Results and discussionA total of 160 metabolites were alternatively identified definitely or tentatively, which were significantly different in various plant parts by multivariate statistical analysis. Quantitative analysis showed that underutilized plant parts also contain many active ingredients. Compared with the medicinal part of root bark, the root core part still contains a higher content of paeoniflorin (17.60 ± 0.06 mg/g) and PGG (15.50 ± 2.00 mg/g). Petals, as an edible part, contain high levels of quercitrin, and stamens have higher methyl gallate and PGG. Unexpectedly, the ovary has the highest content of methyl gallate and rather high levels of PGG (38.14 ± 1.27 mg/g), and it also contains surprisingly high concentrations of floralalbiflorin I. Paeoniflorin (38.68 ± 0.76 mg/g) is the most abundant in leaves, and the content is even higher than in the root bark. Branches are also rich in a variety of catechin derivatives and active ingredients such as hydrolyzable tannins. Seed kernels also contain fairly high levels of paeoniflorin and albiflorin. Fruit shells still contain a variety of components, although not at high levels. Seed coats, as by-products removed from peony seeds before oil extraction, have high contents of stilbenes, such as trans-gnetin H and suffruticosol B, showing significant potential for exploitation. Except for the seed kernels, extracts obtained from other parts exhibited good antioxidant activity in DPPH, ABTS, and ferric ion reducing antioxidant power (FRAP) assays (0.09–1.52 mmol TE/g). Five compounds (gallic acid, PGG, trans-resveratrol, kaempferol, and quercitrin) were important ingredients that contributed to their antioxidant activities. Furthermore, P. ostii seed cakes were first reported to possess agonistic activity toward CB1/CB2 receptors. This study provides a scientific basis for the further development and utilization of P. ostii plant resources.

IntroductionAlthough several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear.MethodsWe performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA.ResultsIn the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed.DiscussionIn conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

BackgroundThis open, observational clinical study aimed to investigate the efficacy, safety and survival outcomes of neoadjuvant chemotherapy, neoadjuvant immunotherapy with(out) chemotherapy and neoadjuvant targeted therapy among resectable stage III non-small cell lung cancer (NSCLC) patients (NCT04197076) in real world. 48 of the 57 evaluable patients were included in this interim analysis.MethodsThis study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years or older and had resectable clinical stage III disease. Surgical resection was conducted after neoadjuvant chemotherapy (13 patients), immunotherapy with(out) chemotherapy (26 patients), and targeted therapy (9 patients). Disease-free survival (DFS) was evaluated as the primary endpoint. The secondary endpoint was pathological complete response (pCR) rate. Clinical response rate (cRR), related adverse events (AEs), surgical feasibility and pathological features were also discussed in this study.ResultsSignificant differences in DFS were noted between chemotherapy and immunotherapy [7.7 months (range, 3.1 to 23.2 months) vs. 9.6 months (range, 4.0 to 47.9 months); P=0.032], and between chemotherapy and targeted therapy [7.7 months (range, 3.1 to 23.2 months) vs. 13.2 months (range, 7.5 to 32.2 months); P=0.015], but not between immunotherapy and targeted therapy (P=0.500). Subgroup analysis also favored neoadjuvant immunotherapy and targeted therapy. 5 patients achieved pathological complete response (pCR), all of whom were in the neoadjuvant immunotherapy arm, leading to a pCR rate of 19.2% in this arm. Treatment-emergent adverse events (TEAEs) of over grade 3 occurred in 11 patients (19.3%), with 5 (29.4%) in the chemotherapy arm, 5 (16.7%) in the immunotherapy arm and 1 (10.0%) in the targeted therapy arm. One grade 4 and one grade 2 surgery-related serious adverse event occurred in the neoadjuvant chemotherapy and immunotherapy arm, respectively.ConclusionIn patients diagnosed with resectable stage III NSCLC, neoadjuvant immunotherapy and neoadjuvant targeted therapy were associated with significantly longer disease-free survival compared with neoadjuvant chemotherapy. Clinical and pathological response rates were also higher in the immunotherapy and targeted therapy arm. Adverse events were found to be manageable and similar across all three groups, and surgical feasibility favored immunotherapy or targeted therapy rather than chemotherapy.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04197076.

BackgroundIn this study, we developed and validated machine learning (ML) models by combining radiomic features extracted from magnetic resonance imaging (MRI) with clinicopathological factors to assess pulmonary nodule classification for benign malignant diagnosis.MethodsA total of 333 consecutive patients with pulmonary nodules (233 in the training cohort and 100 in the validation cohort) were enrolled. A total of 2,824 radiomic features were extracted from the MRI images (CE T1w and T2w). Logistic regression (LR), Naïve Bayes (NB), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) classifiers were used to build the predictive models, and a radiomics score (Rad-score) was obtained for each patient after applying the best prediction model. Clinical factors and Rad-scores were used jointly to build a nomogram model based on multivariate logistic regression analysis, and the diagnostic performance of the five prediction models was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsA total of 161 women (48.35%) and 172 men (51.65%) with pulmonary nodules were enrolled. Six important features were selected from the 2,145 radiomic features extracted from CE T1w and T2w images. The XGBoost classifier model achieved the highest discrimination performance with AUCs of 0.901, 0.906, and 0.851 in the training, validation, and test cohorts, respectively. The nomogram model improved the performance with AUC values of 0.918, 0.912, and 0.877 in the training, validation, and test cohorts, respectively.ConclusionMRI radiomic ML models demonstrated good nodule classification performance with XGBoost, which was superior to that of the other four models. The nomogram model achieved higher performance with the addition of clinical information.

Although significant progress has been made in developing autonomous vehicle technology, further research is still needed to reduce the risk of collision by planning a suitable path. Drawing vehicle paths through pedestrian collision avoidance action is worth further study. In this paper, vehicle path planning considering pedestrian collision avoidance action is proposed to improve vehicle driving safety further. First, the movement features reflecting different types of pedestrian collision avoidance intention are summarized through the actual human-vehicle collision accident video. Then, the data representing the pedestrian action features are obtained through the deep neural network and input into the trained Hidden Markov Model to predict pedestrian intention. Finally, the vehicle collision avoidance path is planned through the cubic polynomial combined with the pedestrian intention. The algorithm is verified through the pedestrian collision avoidance action in the simulation scene. The results show that this algorithm can predict the intention of different types of pedestrians to avoid collisions at frames 9, 8, and 10, respectively, which is 0.6 seconds, 0.4 seconds, and 0.6 seconds faster than the Long Short Term Memory algorithm. Finally, a suitable path is planned, and the collision was successfully avoided.

Abstract Mutations in the Presenilin genes (PSEN1 and PSEN2) are the major cause of familial Alzheimer’s disease (AD), highlighting the importance of Presenilin (PS) in AD pathogenesis. Previous studies of PS function in the hippocampus demonstrated that loss of PS results in the impairment of short- and long-term synaptic plasticity and neurotransmitter release at hippocampal Schaffer collateral (SC) and mossy fiber (MF) synapses. Cortical input to the hippocampus through the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) is critical for normal cognitive functions and is particularly vulnerable during aging and early stages of AD. Whether PS regulates synaptic function in the perforant pathways, however, remained unknown. In the current study, we investigate PS function in the LPP and MPP by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from postnatal forebrain-restricted excitatory neuron-specific PS conditional double knockout (cDKO) mice. We found that paired-pulse ratio (PPR) is reduced in the LPP and MPP of PS cDKO mice. Moreover, synaptic frequency facilitation or depression in the LPP or MPP, respectively, is impaired in PS cDKO mice. Notably, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) minics and occludes the effects of PS inactivation, as evidenced by decreases of the evoked excitatory postsynaptic currents (EPSCs) amplitude in the LPP and MPP of control neurons but no effect on the EPSC amplitude in PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the observed deficits in synaptic transmission. While spontaneous synaptic events, such as both the frequency and the amplitude of spontaneous or miniature EPSCs, are similar between PS cDKO and control neurons, long-term potentiation (LTP) is impaired in the LPP and MPP of PS cDKO mice, accompanied with reduction of evoked NMDA receptor-mediated responses. These findings show the importance of PS in the regulation of synaptic plasticity and intracellular calcium homeostasis in the hippocampal perforant pathways.

Abstract Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.

Abstract Spray-induced gene silencing (SIGS) can inhibit plant diseases by topical application of double- (dsRNA) or single-stranded (sRNA) RNA molecules onto plants to silence virulence-related pathogen genes. However, the on-field application of SIGS is limited by the instability of naked RNA and low RNA uptake by pathogens. Nanoparticles have been used as RNA carriers to enhance RNA silencing. Rice sheath blight caused by Rhizoctonia solani (R. solani) is one of the most devastating fungal diseases in rice (Oryza sativa L.). In this study, we aimed to explore the protective effects of nanoparticle-delivered dsRNA against rice sheath blight. The key pathogenic genes, RsAGO1 and RsAGO2, of R. solani were screened as targets for dsRNA. Chitosan (CS), polyethyleneimine (PEI), protamine, carbon quantum dot (CQD), polyamidoamine (PAMAM), and chitosan/SPc complex (CSC) were selected as dsRNA carriers. All the evaluated nanoparticles could assemble with dsRNA to form nanoparticle-dsRNA complexes, and CQD and CSC showed improved dsRNA load capacity. Particularly, CSC could enhance the stability of dsRNA and cause a 7% reduction in fluorescence intensity after nuclease treatment. CSC and CS effectively enhanced the efficiency of dsRNA uptake by pathogens. Furthermore, CSC could reduce pathogen infection and prolong the protection time of dsRNA by up to 20 days. Overall, this study provides a novel and efficacious SIGS-based strategy for producing RNA-based fungicides.

Objectives: This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50–85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 ​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Results: Of the 448 randomized patients, 409 (LY06006, n ​= ​311; placebo, n ​= ​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P ​

The properties of single shear specimens connected by wooden nail frictional welding and twist nails were studied. The single shear properties of the specimens connected by wooden nail welding were lower than that of the twist nail specimens. The single shear capacity of the wooden nail welding specimen was determined by calculating the method of design value of the bearing capacity of the pin connection. Furthermore, the flexural properties of the wooden nail welding laminated timber were analyzed. Due to the larger diameter of the wooden nails compared with the twist nails, the wooden nail welding laminated timber in the elastic phase had higher stiffness. The elastic modulus of the wooden nail welding laminated timber exceeded the average elastic modulus of the constituent lumber pieces by 9.46%. The number of wood lumbers in wooden nail welding laminated timber had little effect on the elastic modulus of laminated timber, but the nail spacing had a certain effect. Therefore, in future research, it is recommended to use the construction method of twist nail connection to design the wooden nail welding laminated timber. In addition, the nail spacing should refer to the GB 50005 (2003) standard and the wood structure design manual.

Three kinds of L-shaped latticed joint were designed to study the shear bearing capacity of joints prepared by welding of wooden dowels prepared with self-tapping screws. The results showed that such composite dowels in all specimens showed varying degrees of bending and splitting on the surface of the beech dowel after the shear test. The bending bearing capacity of the joint was the bending moment at the geometric center of the four composite dowels. The shear force of each composite dowel generated from the bending moment was equal with the same direction. The ultimate standard value of the theoretical loading force (F) was equal to 4.44 kN and the calculated design value (Fd) was equal to 2.96 kN. The errors between the standard and design value and test value of 3.94 kN were 11.2% and 24.9%, respectively. The theoretical value was relatively consistent with the test value. If the calculated design value was applied to estimate the ultimate bearing capacity of the joint, it was on the conservative side.

Abstract Background Nanomaterials are widely used as pesticide adjuvants to increase pesticide efficiency and minimize environmental pollution. But it is increasingly recognized that nanocarrier is a double-edged sword, as nanoparticles are emerging as new environmental pollutants. This study aimed to determine the biotoxicity of a widely applied star polycation (SPc) nanocarrier using Drosophila melanogaster, the fruit fly, as an in vivo model. Results The lethal concentration 50 (LC50) value of SPc was identified as 2.14 g/L toward third-instar larvae and 26.33 g/L for adults. Chronic exposure to a sub lethal concentration of SPc (1 g/L) in the larval stage showed long-lasting adverse effects on key life history traits. Exposure to SPc at larval stage adversely impacted the lifespan, fertility, climbing ability as well as stresses resistance of emerged adults. RNA-sequencing analysis found that SPc resulted in aberrant expression of genes involved in metabolism, innate immunity, stress response and hormone production in the larvae. Orally administrated SPc nanoparticles were mainly accumulated in intestine cells, while systemic responses were observed. Conclusions These findings indicate that SPc nanoparticles are hazardous to fruit flies at multiple levels, which could help us to develop guidelines for further large-scale application.

Abstract Background Disordered lipid metabolism plays an essential role in both the initiation and progression of alcoholic fatty liver disease (AFLD), and fatty acid β-oxidation is increasingly considered as a crucial factor for controlling lipid metabolism. Hif-2α is a member of the Hif family of nuclear receptors, which take part in regulating hepatic fatty acid β-oxidation. However, its functional role in AFLD and the underlying mechanisms remain unclear. Results Hif-2α was upregulated in EtOH-fed mice and EtOH-treated AML-12 cells. Inhibition or silencing of Hif-2α led to increased fatty acid β-oxidation and BNIP3-dependent mitophagy. Downregulation of Hif-2α activates the PPAR-α/PGC-1α signaling pathway, which is involved in hepatic fatty acid β-oxidation, by mediating BNIP3-dependent mitophagy, ultimately delaying the progression of AFLD. Conclusions Hif-2α induces liver steatosis, which promotes the progression of AFLD. Here, we have described a novel Hif-2α-BNIP3-dependent mitophagy regulatory pathway interconnected with EtOH-induced lipid accumulation, which could be a potential therapeutic target for the prevention and treatment of AFLD.

This study aimed to explore the potential molecular mechanisms of acupuncture in the adjuvant treatment of infertility. A rat model of ovulation induction was constructed using horse serum gonadotropin and human chorionic gonadotropin, and then acupuncture was used to treat the model rats at Guanyuan and Sanyinjiao points. Hematoxylin eosin (HE) staining, the endometrial thickness, and enlargement of uterine cavity were determined to evaluate the effects of acupuncture on the uterus of ovulation induction rats. Meanwhile, the uterus tissues were sent for gene microarray analyses. Acupuncture enhanced the endometrial receptivity of ovulation induction rats. Gene microarray showed that 189 overlapped differential expressed genes (DEGs) were identified, and these overlapped DEGs were divided into four clusters by Mfuzz algorithm. Afterwards, interaction networks containing 842 interaction pairs were established, and the DEGs in the interaction networks were significantly enriched in 20 BP and 10 KEGG pathways, including wound healing, response to glucocorticoid, TNF signaling pathway, terpenoid backbone biosynthesis, and glutathione metabolism. By calculating topological parameters, Anxa5, Casp8, Tgm2, Frk, Mmp7, Timp1, Hmgcr, Cth, Serpinal, and Abcbla were the important hub genes of the interaction networks. Our findings revealed the changes at transcriptome levels related to ovulation induction and acupuncture protection therapy.

Abstract Background Intratumoral heterogeneity is the primary challenge in the treatment of glioblastoma (GBM). The presence of glioma stem cells (GSCs) and their conversion between different molecular phenotypes contribute to the complexity of heterogeneity, culminating in preferential resistance to radiotherapy. ARP2/3 (actin-related protein-2/3) complexes (ARPs) are associated with cancer migration, invasion and differentiation, while the implications of ARPs in the phenotype and resistance to radiotherapy of GSCs remain unclear. Methods We screened the expression of ARPs in TCGA-GBM and CGGA-GBM databases. Tumor sphere formation assays and limiting dilution assays were applied to assess the implications of ARPC1B in tumorigenesis. Apoptosis, comet, γ-H2AX immunofluorescence (IF), and cell cycle distribution assays were used to evaluate the effect of ARPC1B on radiotherapy resistance. Immunoprecipitation (IP) and mass spectrometry analysis were used to detect ARPC1B-interacting proteins. Immune blot assays were performed to evaluate protein ubiquitination, and deletion mutant constructs were designed to determine the binding sites of protein interactions. The Spearman correlation algorithm was performed to screen for drugs that indicated cell sensitivity by the expression of ARPC1B. An intracranial xenograft GSC mouse model was used to investigate the role of ARPC1B in vivo. Results We concluded that ARPC1B was significantly upregulated in MES-GBM/GSCs and was correlated with a poor prognosis. Both in vitro and in vivo assays indicated that knockdown of ARPC1B in MES-GSCs reduced tumorigenicity and resistance to IR treatment, whereas overexpression of ARPC1B in PN-GSCs exhibited the opposite effects. Mechanistically, ARPC1B interacted with IFI16 and HuR to maintain protein stability. In detail, the Pyrin of IFI16 and RRM2 of HuR were implicated in binding to ARPC1B, which counteracted TRIM21-mediated degradation of ubiquitination to IFI16 and HuR. Additionally, the function of ARPC1B was dependent on IFI16-induced activation of NF-κB pathway and HuR-induced activation of STAT3 pathway. Finally, we screened AZD6738, an ataxia telangiectasia mutated and rad3-related (ATR) inhibitor, based on the expression of ARPC1B. In addition to ARPC1B expression reflecting cellular sensitivity to AZD6738, the combination of AZD6738 and radiotherapy exhibited potent antitumor effects both in vitro and in vivo. Conclusion ARPC1B promoted MES phenotype maintenance and radiotherapy resistance by inhibiting TRIM21-mediated degradation of IFI16 and HuR, thereby activating the NF-κB and STAT3 signaling pathways, respectively. AZD6738, identified based on ARPC1B expression, exhibited excellent anti-GSC activity in combination with radiotherapy.

Abstract Background This scoping review reports on studies that collect survey data using quantitative research to measure self-reported oral health status outcome measures. The objective of this review is to categorize measures used to evaluate self-reported oral health status and oral health quality of life used in surveys of general populations. Methods The review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) with the search on four online bibliographic databases. The criteria include (1) peer-reviewed articles, (2) papers published between 2011 and 2021, (3) only studies using quantitative methods, and (4) containing outcome measures of self-assessed oral health status, and/or oral health-related quality of life. All survey data collection methods are assessed and papers whose methods employ newer technological approaches are also identified. Results Of the 2981 unduplicated papers, 239 meet the eligibility criteria. Half of the papers use impact scores such as the OHIP-14; 10% use functional measures, such as the GOHAI, and 26% use two or more measures while 8% use rating scales of oral health status. The review identifies four data collection methods: in-person, mail-in, Internet-based, and telephone surveys. Most (86%) employ in-person surveys, and 39% are conducted in Asia-Pacific and Middle East countries with 8% in North America. Sixty-six percent of the studies recruit participants directly from clinics and schools, where the surveys were carried out. The top three sampling methods are convenience sampling (52%), simple random sampling (12%), and stratified sampling (12%). Among the four data collection methods, in-person surveys have the highest response rate (91%), while the lowest response rate occurs in Internet-based surveys (37%). Telephone surveys are used to cover a wider population compared to other data collection methods. There are two noteworthy approaches: 1) sample selection where researchers employ different platforms to access subjects, and 2) mode of interaction with subjects, with the use of computers to collect self-reported data. Conclusion The study provides an assessment of oral health outcome measures, including subject-reported oral health status and notes newly emerging computer technological approaches recently used in surveys conducted on general populations. These newer applications, though rarely used, hold promise for both researchers and the various populations that use or need oral health care.

The goal of this study was to see how effective and safe neoadjuvant chemoradiation with image-guided IMRT was in patients with locally advanced resectable gastric cancer. Between January 2013 and June 2019, patients with locally advanced (cT3/cT4 or N+) gastric cancer treated with neoadjuvant chemoradiotherapy at PUMCH (Peking Union Medical College Hospital) were retrospectively studied. Using concurrent chemotherapy (Capecitabine alone or XELOX*2 cycles), radiotherapy (IMRT (intensity-modulated radiation therapy) 45 Gy, 25#, 5 weeks) was delivered with IGRT (image-guided radiotherapy) before the start of each weeks therapy to ensure accuracy and repeatability. A total of 95 patients were enrolled in the study, 93 (97.9%) stage cT3/T4 and 85 (89.5%) stage N+. Of these, 85 patients (89.5%) had a tumor located in the upper 1/3 of the stomach, and 93/95 patients (97.9%) completed neoadjuvant chemoradiation, with 80 patients (84.2%) undergoing stomach resection (58 D2 and 22 D1 gastrostomies). Pathology downstaging was found in 68 patients (85.0%), with 66 patients (82.5%) receiving T downstaging and 56 patients (70.0%) receiving N downstaging. There were 11 individuals (13.8%) who had a pathological complete response (PCR). The average period of follow-up was 44.7 months (19–96 months). The 5-year OS (overall survival), LRFS (local recurrence-free survival), and DMFS (distant metastasis free survival) rates of patients were 47.0% (95% CI: 38.6–55.4), 86.55% (95% CI: 79.1–93.99) and 60.71% (95% CI: 51.49–69.93%), respectively. Thirteen (13.7%) patients had grade 3–4 leukopenia, anemia, and thrombocytopenia, while 9 (9.5%) patients had grade 3–4 anemia, and 5 (5.3%) patients had grade 3–4 thrombocytopenia. PCR was found to be a significant predictive factor for OS in multivariate analysis (HR = 11.211, 95% CI: 1.500–83.813, p = 0.024). The method of using IGRT image-guided IMRT (45 Gy, 25 fractions, 5 weeks) combined with concurrent chemotherapy in patients with locally advanced resectable gastric cancer was equally effective when compared to the clinical efficacy of neoadjuvant chemoradiotherapy, with clinical outcomes achieving equal efficacy, with similar PCR rates and high rates of OS, LRFS, and DMFS, as well as good tolerances of concurrent chemoradiotherapy with acceptable side effects.

Abstract Background The lack of standardized delineation of lymph node station in lung cancer radiotherapy leads to nonstandard clinical target volume (CTV) contouring, especially in patients with bulky lump gross target volume lymph nodes (GTVnd). This study defines lymph node region boundaries in radiotherapy for lung cancer and automatically contours lymph node stations based on the International Association for the Study of Lung Cancer (IASLC) lymph node map. Methods Computed tomography (CT) scans of 200 patients with small cell lung cancer were collected. The lymph node zone boundaries were defined based on the IASLC lymph node map, with adjustments to meet radiotherapy requirements. Contours of lymph node stations were confirmed by two experienced oncologists. A model (DiUNet) was constructed by incorporating the contours of GTVnd to precisely contour the boundaries. Quantitative evaluation metrics and clinical evaluations were conducted. Results The mean 3D Dice similarity coefficient (Dice similarity coefficient) values of DiUNet in most lymph node stations was greater than 0.7, 98.87% of the lymph node station slices are accepted. The mean DiUNet score was not significantly different from that of the man contoured in the evaluation of lymph node stations and CTV. Conclusion This is the first study to propose a method that automatically contours lymph node regions station by station based on the IASLC lymph node map with bulky lump GTVnd. Delineation of lymph node stations based on the DiUNet model is a promising strategy to obtain accuracy and efficiency for CTV delineation in lung cancer patients, especially for bulky lump GTVnd.

Bacterial cells utilize cholesterol-enhanced pore formation to specifically target eukaryotic cells. Here, the authors present a class of bio-inspired, cholesterol-enhanced nanopores which display anticancer activities in vitro.

Introduction: Cannabinoids including cannabidiol (CBD) have attracted enormous interest as bioactive ingredients for various dermatological and/or cosmeceutical uses. However, topical applications of cannabinoids might be limited without a fundamental understanding of their skin permeability. Herein, we aimed to evaluate the skin permeability of CBD and its topical formulations using artificial skin membrane assays. The solubility and stability of CBD in various surfactants that are commonly used in topical applications were also evaluated. Methods: CBD and two CBD-incorporated topical formulations (cream and gel) were prepared for this study. Computational predictions (SwissADME and DERMWIN™) and the parallel artificial membrane permeability assay (PAMPA) were used to evaluate the skin permeability of CBD isolate. The Franz cell diffusion (in vitro release testing) assay was used to evaluate the skin permeability of CBD formulations. The solubility and stability of CBD in surfactants were assessed by high-performance liquid chromatography and mass spectrometry analysis. Results: CBD isolate showed favorable skin permeability in the SwissADME and DERMWIN™ predictions (−Log Kp of 3.6 and 5.7 cm/s, respectively) and PAMPA (−LogPe value of 5.0 at pH of 6.5 and 7.4). In addition, CBD had higher solubility (378.4 μg/mL) in surfactant Tween 20 as compared to its solubility in polyisobutene. In an acidic environment (pH 5 and 6), Tween 20 maintained the CBD content at 81% and 70% over 30 days, respectively. CBD in the formulations of cream and gel also had moderate skin permeability in the Franz cell diffusion assay. Conclusion: Data from artificial membrane-based assays support that CBD is a skin permeable cannabinoid and the permeability and stability of its formulations may be influenced by several factors such as surfactant and pH environment. Findings from our study suggest that CBD may have suitable skin permeability for the development of dermatological and/or cosmeceutical applications but further studies using in vivo models are warranted to confirm this.

Abstract Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development. To better understand the pathological mechanisms of OA, new approaches, methods, and techniques need to be used to understand OA pathogenesis. In this review, we first focus on the epigenetic regulation of OA, with a particular focus on DNA methylation, histone modification, and microRNA regulation, followed by a summary of several key mediators in OA-associated pain. We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain, such as CRISPR, scRNA sequencing, and lineage tracing. Next, we discuss the timely updates concerning cell death regulation in OA pathology, including pyroptosis, ferroptosis, and autophagy, as well as their individual roles in OA and potential molecular targets in treating OA. Finally, our review highlights new directions on the role of the synovial lymphatic system in OA. An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

Abstract Background Anastomotic blood supply is vital to anastomotic healing. The aim of this study was to demonstrate the effect of the left colic artery (LCA) on blood supply in the anastomotic area, explore the relationship between individual differences in the LCA and blood supply in the anastomotic area, and elucidate the relevant indications for LCA retention during radical resection for sigmoid or rectal cancer. Method Radical sigmoid or rectal cancer resection with LCA retention was performed in 40 patients with colorectal cancer who participated in this study. Systemic pressure, LCA diameter, and the distance from the root of the LCA to the root of the inferior mesenteric artery were measured and recorded. The marginal artery stump pressure in the anastomotic colon before and after the LCA clamping was measured, respectively. Results There is a significant difference between the marginal artery stump pressure before LCA ligation and after ligation (53.1 ± 12.38 vs 42.76 ± 12.71, p < 0.001). The anastomotic blood supply positively and linearly correlated with body mass index and systemic pressure. Receiver-operating curve analysis revealed that LCA diameter (area under the curve 0.971, cutoff 1.95 mm) was an effective predictor of LCA improving anastomosis blood supply. No relationship was found between the LCA root location and anastomotic blood supply. Conclusion Preserving the LCA is effective in improving blood supply in the anastomotic area, and larger LCA diameters result in a better blood supply to the anastomotic area.

Abstract Background Prevalent single-cell transcriptomic profiling (scRNA-seq) methods are mainly based on the synthesis and enrichment of full-length double-stranded complementary DNA. These approaches are challenging to generate accurate quantification of transcripts when their abundance is low or their full-length amplifications are difficult. Results Based on our previous finding that Tn5 transposase can directly cut-and-tag DNA/RNA hetero-duplexes, we present SHERRY2, a specifically optimized protocol for scRNA-seq without second-strand cDNA synthesis. SHERRY2 is free of pre-amplification and eliminates the sequence-dependent bias. In comparison with other widely used scRNA-seq methods, SHERRY2 exhibits significantly higher sensitivity and accuracy even for single nuclei. Besides, SHERRY2 is simple and robust and can be easily scaled up to high-throughput experiments. When testing single lymphocytes and neuron nuclei, SHERRY2 not only obtained accurate countings of transcription factors and long non-coding RNAs, but also provided bias-free results that enriched genes in specific cellular components or functions, which outperformed other protocols. With a few thousand cells sequenced by SHERRY2, we confirmed the expression and dynamics of Myc in different cell types of germinal centers, which were previously only revealed by gene-specific amplification methods. Conclusions SHERRY2 is able to provide high sensitivity, high accuracy, and high throughput for those applications that require a high number of genes identified in each cell. It can reveal the subtle transcriptomic difference between cells and facilitate important biological discoveries.

Abstract Background Dexmedetomidine has controversial influence on cardiac electrophysiology. The aim of this study was to explore the effects of dexmedetomidine on perioperative cardiac electrophysiology in patients undergoing general anesthesia. Methods Eighty-one patients were randomly divided into four groups: groups D1, D2, D3 receiving dexmedetomidine 1, 1, 0.5 μg/kg over 10 min and 1, 0.5, 0.5 μg/kg/h continuous infusion respectively, and control group (group C) receiving normal saline. Twelve-lead electrocardiograms were recorded at the time before dexmedetomidine/normal saline infusion (T1), loading dose finish (T2), surgery ending (T6), 1 h (T7) after entering PACU, 24 h (T8), 48 h (T9), 72 h (T10) and 1 month (T11) postoperatively. Cardiac circulation efficiency (CCE) were also recorded. Results Compared with group C, QTc were significantly increased at T2 in groups D1 and D2 while decreased at T7 and T8 in group D3 (P

BackgroundThe cancer screening rate in the working population is very low in China. Information-motivation-behavioral skills (IMB) model has been applied to elucidate screening behavior for various chronic diseases but has not been investigated in analyzing cancer screening behavior. This study aimed to examine factors influencing cancer screening behavior and their linkages based on the IMB model.MethodsA cross-sectional study was conducted in Shanghai, China from August to October 2021. Data were obtained through an anonymous questionnaire. Predictive relationships between variables in the IMB model and cancer screening behavior were evaluated. Structural equation modeling (SEM) was constructed to demonstrate the utility of the IMB model.ResultsAmong the 556 participants included in the analysis, 34.4% of participants had ever done a cancer screening. The construct validation analysis supported that the measure items included were acceptable. SEM found that knowledge of cancer warning signs and symptoms (β = 0.563, p

Bacterial infections are a serious public health issue that threatens the lives of patients because of their ability to induce other lethal complications without prompt treatment. Conventional antibiotic therapy can cause bacterial resistance and other adverse effects. It is highly desirable to develop effective and antibiotic‐independent therapeutic strategies to treat various kinds of bacterial infections. Herein, sonodynamic‐enhanced piezoelectric materials MoS2 and Cu2Oheterostructure that responds to exogenous ultrasound (US) and generates reactive oxygen for Staphylococcus aureus elimination are developed. It is shown in the results that the polariton charge induced by piezoelectric MoS2 nanosheets under US irradiation can accelerate the transfer of electric in Cu2O. Furthermore, US irradiation induces valence conversion from Cu(I) to Cu(II), which can accelerate glutathione oxidation significantly and destroy the bacterial antioxidant defense system. Hence, the as‐prepared piezoelectric‐enhanced sonosensitizer possesses a highly effective antibacterial efficacy of 99.85% against S. aureus under US irradiation for 20 min, with good biocompatibility. Herein, effective ultrasonic piezocatalytic therapy is offered through constructing heterogeneous interfaces with ultrasonic piezoelectric response.