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Abstract Modern offshore and onshore green energy engineering includes energy harvesting—as a result, extensive experimental investigations, as well as safety and reliability analysis are crucial for design and engineering. For this study, several wind-tunnel experiments under realistic in situ wind speed conditions have been conducted to examine the performance of galloping energy harvester. Next, a novel structural reliability approach is presented here that is especially well suited for multi-dimensional energy harvesting systems that have been either numerically simulated or analog observed during the representative time lapse, yielding an ergodic system time record. As demonstrated in this study, the advocated methodology may be used for risk assessment of dynamic system structural damage or failure. Furthermore, traditional reliability methodologies dealing with time series do not easily cope with the system’s high dimensionality, along with nonlinear cross-correlations between the system’s components. This study’s objective was to assess state-of-the-art reliability method, allowing efficient extraction of relevant statistical information, even from a limited underlying dataset. The methodology described in this study aims to assist designers when assessing nonlinear multidimensional dynamic energy harvesting system’s failure and hazard risks.

Abstract Background Vitamin D deficiency (VDD) is a public health problem. The variation in vitamin D status across regions and populations remains unclear, and there is a lack of consensus regarding the screening for VDD in individuals. Methods Children who visited the hospital from January 2019 to December 2020 were included in this study. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using an enzyme-linked immunosorbent assay. The cutoffs for serum 25(OH)D concentrations to define deficiency, insufficiency, and sufficiency were

Macadamia nut polypeptides were prepared by enzymatic hydrolysis of macadamia nut meal, and suitable proteases for the preparation of macadamia antioxidant polypeptides were screened with ABTS+ radical scavenging effects as evaluation indicators. Four constituents (MNAP-1, MNAP-2, MNAP-3, MNAP-4) were obtained by DA201-C macroporous resin and dialysis technology. The scavenging capacity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·), hydroxyl radical and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonate radicals) radical (ABTS+·), and reducing power were investigated by comparing with glutathione as controls. The results showed that the suitable protease was complex protease for the preparation of macadamia antioxidant polypeptides, which was better than neutral protease, acid protease, alkaline protease, papain and bromelain at the same concentration. Antioxidant activities of different molecular weight macadamia nut polypeptides were different, which all had strong scavenging capacity against DPPH and ABTS+ radicals, and also had certain scavenging capacity against hydroxyl radical and reducing power. MNAP-4 (molecular weight less than 1000 Da) had the strongest scavenging capacity against DPPH, ABTS+ and hydroxyl radicals and the highest reducing power with half maximal inhibitory concentration (IC50) of 0.36, 6.75, 0.08 and 3.19 mg/mL, respectively, which was lower than other molecular weight polypeptides. Correlation analysis showed different molecular weight macadamia nut polypeptides had good correlations with their DPPH, hydroxyl and ABTS+ radicals scavenging capacity and reducing power with r values of 0.947, 0.964, 0.948 and 0.856 (P

Abstract Background Nonsecretory multiple myeloma (NSMM) is a rare type of multiple myeloma (MM). Few studies have described the clinical features and outcomes of NSMM in novel agents. Additionally, the prognostic characteristics have remained controversial in recent years. Purpose To investigate the clinical and prognostic features of NSMM and explore the prognostic value of involved free light chain (FLC) levels in NSMM patients in the Chinese population. Methods We retrospectively enrolled 176 newly diagnosed NSMM cases between January 2005 and December 2021 from 19 clinical centers in China. The control group was selected using a 1:4 propensity score matching technique of newly diagnosed secretory MM, with age, sex and diagnosis time as the matching variables. Results The median age of NSMM patients was 60 years, and 22.6% of patients were classified as ISS stage 3. The ORR of the NSMM patients was 87.4%, and the CR was 65.8%. Compared to the matched secretory MM patients, more NSMM patients achieved CR after first-line treatment (65.8% vs. 36%, p = 0.000). The ORR of first-line treatment was not significantly different between NSMM and secretory MM (89.45% vs. 84.7%, p = 0.196). The first-line PFS was 27.5 m and 23 m (p = 0.063), and the median OS was 81 m and 70 months (p = 0.401). However, for CR-achieved NSMM and CR-not-achieved NSMM patients, the median PFS was 37 m vs. 16 m (p = 0.021), while the median OS showed no difference (107 m vs. 87 m, p = 0.290). In multivariate analysis, the significant factors for PFS were age ≥ 65 and ISS-3. ISS-3 was the only independent prognostic factor of OS. The iFLC ≥ 50 mg/L group had a high ORR of 97.3%, and the median PFS and OS were 48 m and NR, respectively. Compared to the matched secretory MM, the iFLC ≥ 50 mg/L group also showed more CR and longer OS (NR vs. 70 m, p = 0.006) and PFS (48 m vs. 23 m, p = 0.003). Conclusions Our results revealed that Chinese NSMM patients are younger and have a higher CR but not superior survival. The subgroup of NSMM patients with iFLC ≥ 50 mg/L had better outcomes than secretory MM.

We report the clonal spread and evolution of high-risk Pseudomonas aeruginosa sequence type 463 co-producing KPC-2 and AFM-1 carbapenemases isolated from hospital patients in China during 2020–2022. Those strains pose a substantial public health threat and surveillance and stricter infection-control measures are essential to prevent further infections.

To date, few studies have investigated whether the RNA-editing enzymes adenosine deaminases acting on RNA (ADARs) influence RNA functioning in lung adenocarcinoma (LUAD). To investigate the role of ADAR in lung cancer, we leveraged the advantages of The Cancer Genome Atlas (TCGA) database, from which we obtained transcriptome data and clinical information from 539 patients with LUAD. First, we compared ARAR expression levels in LUAD tissues with those in normal lung tissues using paired and unpaired analyses. Next, we evaluated the influence of ADARs on multiple prognostic indicators, including overall survival at 1, 3 and 5 years, as well as disease-specific survival and progression-free interval, in patients with LUAD. We also used Kaplan-Meier survival curves to estimate overall survival and Cox regression analysis to assess covariates associated with prognosis. A nomogram was constructed to validate the impact of the ADARs and clinicopathological factors on patient survival probabilities. The volcano plot and heat map revealed the differentially expressed genes associated with ADARs in LUAD. Finally, we examined ADAR expression versus immune cell infiltration in LUAD using Spearman's analysis. Using the Gene Expression Profiling Interactive Analysis (GEPIA2) database, we identified the top 100 genes most significantly correlated with ADAR expression, constructed a protein-protein interaction network and performed a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis on these genes. Our results demonstrate that ADARs are overexpressed in LUAD and correlated with poor patient prognosis. ADARs markedly increase the infiltration of T central memory, T helper 2 and T helper cells, while reducing the infiltration of immature dendritic, dendritic and mast cells. Most immune response markers, including T cells, tumor-associated macrophages, T cell exhaustion, mast cells, macrophages, monocytes and dendritic cells, are closely correlated with ADAR expression in LUAD.

Abstract Fatigue damage prediction is essential for safety of contemporary offshore energy industrial projects, like offshore wind turbines, that are to be designed for sufficiently long operational period of time, with minimal operational disruptions. Offshore structures being designed to withstand environmental loadings due to winds and waves. Due to accumulated fatigue damage, offshore wind floating turbines may develop material cracks in their critical locations sooner than expected. Dataset needed for an accurate assessment of fatigue damage may be produced by either extensive numerical modeling, or direct measurements. However, in reality, temporal length of the underlying dataset being typically too short to provide an accurate calculation of direct fatigue damage and fatigue life. Hence, the objective of this work is to contribute to the development of novel fatigue assessment methods, making better use of limited underlying dataset. In this study, in-situ environmental conditions were incorporated to assess offshore FWT tower base stresses; then structural cumulative fatigue damage has been assessed. Novel deconvolution extrapolation method has been introduced in this study, and it was shown to be able to accurately predict long-term fatigue damage. The latter technique was validated, using artificially reduced dataset, and resulted in fatigue damage that was shown to be close to the damage, calculated from the full original underlying dataset. Recommended method has been shown to utilize available dataset much more efficiently, compared to direct fatigue estimation. Accurate fatigue assessment of offshore wind turbine structural characteristics is essential for structural reliability, design, and operational safety.

Abstract Colon adenocarcinoma (COAD) is a common malignant tumor, and the role of the protein PFKFB4 in glycolysis and pentose phosphate pathways is crucial. Researchers investigated the clinical significance of PFKFB4 in COAD by studying its expression in 79 tissue samples using immunohistochemistry. We found that PFKFB4 expression was significantly higher in COAD patients, particularly in the sigmoid colon. Interestingly, high PFKFB4 expression was associated with both improved overall survival (OS) and post-progression survival (PPS) in COAD patients. Further analysis revealed that genes associated with PFKFB4 were linked to various metabolic pathways, including amino acid biosynthesis, glycolysis, gluconeogenesis, glucose metabolism, and inflammatory response. PFKFB4 expression also showed correlations with the infiltration of different immune cell types in COAD patients, such as CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), macrophages, neutrophils, dendritic cells, active mast cells, and resting NK cells. Overall, the relationship between PFKFB4 expression and the prognosis of COAD is complex and diverse, possibly playing different roles at different stages of the disease. Moreover, its mechanism might involve interactions with various metabolic pathways and immune infiltration in the tumor microenvironment. These findings provide valuable insights into the potential role of PFKFB4 as a biomarker or therapeutic target in COAD.

BackgroundCivil aviation pilots are actual operators of civil aircraft. Their job operations are directly associated with passenger safety and flight safety. Unsafe aviation operations are related to fatigue caused by poor sleep quality. Recently, with the promotion of China's air transportation business, irregular working hours of civil aviation pilots rise gradually. However, there is still a lack of relevant research on the influence of working conditions on sleep quality in this group.ObjectiveTo explore potential impact factors of sleep quality among civil aviation pilots, for the purposes of improving sleep quality and health level of this group and ensuring aviation flight safety by formulating health management suggestions in a targeted manner.MethodsAll pilots of an aviation company were approached when they visited the Shanghai Hospital of Civil Aviation Administration of China for their health examinations. After informed consent, an online questionnaire survey was conducted. Self-made questionnaires were used to collect information on general conditions, lifestyle, and subjective work stress levels. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. A total of 1204 valid questionnaires were recovered. Statistical analysis was conducted using SPSS 26.0 software.ResultsThere were 410 pilots (16.8%) who reported sleep disorders, including insufficient sleep time, difficulty falling asleep, and poor sleep quality, and 894 pilots (74.3%) who reported moderate to severe work stress. Associations were identified between sleep quality of pilots and work stress or lifestyle indicators (P

Soft scale insects (Hemiptera, Coccidae) are important pests of various agricultural and horticultural crops and ornamental plants. They have negative impacts on agriculture and forestry. The tribe Coccini represents one of the most ancient evolutionary lineages of soft scale insects. However, no complete Coccini mitochondrial genome (mitogenome) is available in public databases. Here, we described the complete mitogenome of Coccus hesperidum L., 1758. The 15,566 bp mitogenome of C. hesperidum had a high A+T content (83.4%) and contained a typical set of 37 genes, with 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and two ribosomal RNA genes (rRNAs). Only seven tRNAs had the typical clover-leaf secondary structure and the remaining tRNAs lacked the DHU arm, TψC arm or both. Moreover, a comparative analysis of all reported scale insect mitogenomes from GenBank database was performed. The mitogenomes of scale insects showed high similarities in base composition and A+T content. Additionally, our phylogenetic analysis confirmed the monophyly of Coccomorpha and revealed that the archaeococcoids were the most basal lineage within Coccomorpha, while Ericerus pela and Didesmococcus koreanus, belonging to Coccidae, were often mixed with Aclerdidae, making Coccidae a paraphyletic group. These findings expand the mitogenome database of scale insects and provide new insights on mitogenome evolution for future studies across different insect groups.

Abstract Background Curdione is a sesquiterpene isolated from Curcumae Rhizoma that possesses high biological activity and extensive pharmacological effects. As a traditional Chinese medicine, Curcumae Rhizoma can inhibit the development of many types of cancer, especially colorectal cancer. However, the anti-colorectal mechanism of its monomer curdione remains unclear. Methods Colorectal cancer (CRC) cells were treated with curdione at doses of 12.5 μM, 25 μM, and 50 μM, and then the cells’ activity was measured with methyl thiazolyl tetrazolium (MTT). Nude mice were administered different doses of curdione subcutaneously and oxaliplatin by tail vein injection, and then hematoxylin–eosin (HE) staining was adopted to examine tumor histology. Moreover, flow cytometry was applied to detect reactive oxygen species in cells and tissues. Kits were employed to detect the levels of iron ions, malondialdehyde, lipid hydroperoxide, and glutathione. Polymerase chain reaction (PCR) and Western blotting were adopted to detect ferroptosis and m6A modification-related factors. A methylation spot hybridization assay was performed to measure changes in overall methylation. SLC7A11 and HOXA13 were measured by MeRIP-qPCR. The shRNA-METTL14 plasmid was constructed to verify the inhibitory effect of curdione on CRC. Results A dose-dependent decrease in activity was observed in curdione-treated cells. Curdione increased the accumulation of reactive oxygen species in CRC cells and tumor tissues, greatly enhanced the levels of malondialdehyde, lipid hydroperoxide and Fe2+, and lowered the activity of glutathione. According to the qPCR and Western blot results, curdione promoted the expression of METTL14 and YTHDF2 in CRC cells and tissues, respectively, and decreased the expression of SLC7A11, SLC3A2, HOXA13, and glutathione peroxidase 4. Additionally, in animal experiments, the curdione-treated group showed severe necrosis of tumor cells, as displayed by HE staining. Furthermore, compared with the control group, levels of m6A modifying factors (namely, SLC7A11 and HOXA13) were increased in the tissues after drug intervention. METTL14 knockdown was followed by an increase in CRC cell activity and glutathione levels. However, the levels of reactive oxygen species, malondialdehyde, and iron ions decreased. The expression levels of SLC7A11, SLC3A2, HOXA13, and GPX4 were all increased after METTL14 knockdown. Conclusion The results suggest that curdione induces ferroptosis in CRC by virtue of m6A methylation.

Abstract The pBRDF model is able to relate the properties of target materials to the polarization information of incident and reflected light, and is an important basis for obtaining polarization information of targets in space. It is an important basis for obtaining target polarization information and polarization detection of space targets. P-G model is the first strictly pBRDF model officially released, but there are still deficiencies. In this paper, we first analyze the assumption framework of the P-G model, derive the imperfections in the framework through the analysis of the assumption framework, and add scattering and phase function to enhance the existing model. On the basis of the existing P-G model and parameter inversion, the output results of the model are compared with the experimental data through simulation, and the results show that the relative error of the target's linear polarizability is reduced under the improved model, which proves the accuracy and precision of the improved model.

Abstract Background Cervical cancer is a common gynecological malignancy. Gene microarray found that TCP11 gene was highly expressed in cervical cancer. However, the effect of TCP11 gene on the proliferation, apoptosis and migration of cervical cancer cells and its underlying molecular mechanisms are unclear. Methods GEPIA database, tissue microarray, western blot and qRT-PCR were used to analyze the expression of TCP11 gene in cervical cancer tissues and cells and its relationship with patients’ survival rate. The cell cycle and apoptosis were detected by flow cytometry, and the expressions of cell cycle and apoptosis related molecules and EMT-related molecules were detected by Western blot and qRT-PCR. Results The results showed that TCP11 gene was highly expressed in cervical cancer tissues and cells compared with normal cervical tissues and cells, and its expression was positively correlated with patients’ survival rate. The results of proliferation and migration assays showed that TCP11 overexpression inhibited the proliferation and migration of HeLa and SiHa cells. The results showed that TCP11 overexpression blocked the cell cycle of HeLa and SiHa cells, decreased the expression of CDK1 and Cyclin B1, and increased the apoptosis and the expression of caspase-3, cleaved-caspase-3 and cleaved-PARP. TCP11 overexpression increased the protein and mRNA expression of EMT-related molecules ZO-1 and E-cadherin. Conversely, TCP11 knockdown promoted the proliferation of HeLa and SiHa cells and the migration of HeLa cells. Conclusions TCP11 overexpression significantly inhibited the occurrence and development of cervical cancer cells, it may be a potentially beneficial biomarker for cervical cancer.

Abstract Background Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson’s disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients. Methods We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects. Results The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the ‘off’ state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6–100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the ‘off’ state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis. Conclusions This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760

Abstract Background Mixed germ cell tumors originating from the fallopian tubes are rarely reported, and high-grade rhabdomyosarcoma with differentiated components is even less common. The non-specific clinical manifestations of this tumor are prone to misdiagnosis, and there is still controversy over the treatment plan for this rare differentiated type, and there are limited reports on the prognosis of related diseases. Case presentation Here, we report a 34-year-old woman who presented to our hospital with abdominal pain for two weeks and aggravated for two days. After completing relevant examinations, she underwent transabdominal resection of large tubal masses on the left side of the tube + pelvic lymph node dissection + abdominal paraaortic lymph node dissection + right ovarian cyst excision + greater omentectomy + multipoint peritoneal biopsy. hematoxylin–eosin (H&E) and immunohistochemical (IHC) staining were performed on the surgically resected specimens to further determine the type and nature of the tumor, and 3 cycles of Bleomycin + Etoposide + Cisplatonum (BEP) chemotherapy and 1 cycle of EP(Etoposide + Cisplatonum) chemotherapy were given after surgery. Conclusion Up to now, regular follow-up of the patient's tumor markers and imaging showed no abnormalities, the general condition is good, and the tumor free survival time has reached 24 months.

Abstract Background Numerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective. Methods In this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries. Results Compared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: − 2.64, p

To evaluate the antioxidant activity and potential of propolis, Tibetan propolis and its simulated digestive juice were analyzed for its chemical composition (contents of total phenolics (TPC) and total flavonoids (TFC)), reducing power and antioxidant activity (hydroxyl radical scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, metal iron chelating activity and lipid peroxidation inhibition ability). The results showed that the contents of TPC and TFC in Tibetan propolis were 7.02% and 10.05%, respectively. The contents of TPC and TFC in simulated digestive juices were diminished. The contents of TPC and TFC in simulated gastric digestive juices (2 h) were 0.43% and 6.43%, respectively. The contents of TPC and TFC in simulated intestinal digestive juices (2 h) were 0.32% and 5.11%, respectively. The highest values of antioxidant activity was achieved at a concentration of 1 mg/mL, and the values of reducing power, hydroxyl radical scavenging activity, DPPH radical scavenging activity, metal iron chelating activity and lipid peroxidation inhibition ability in Tibetan propolis were 0.35, 96.60%, 92.53%, 19.96% and 97.01%, respectively. Reducing power and DPPH radical scavenging activity of simulated gastric digestive juices exhibited an increasing trend, with respect to the undigested sample. The highest values of reducing power and DPPH radical scavenging activity were 0.39 and 95.69%, respectively. Hydroxyl radical scavenging activity, metal iron chelating activity and lipid peroxidation inhibition ability of simulated gastric digestive juices exhibited a decreasing trend, with respect to the undigested sample. Simulated intestinal digestive had higher hydroxyl radical scavenging rates, metal ion chelation rates and lipid peroxidation inhibition rates than simulated gastric digestive, with highest values of 99.72%, 69.26% and 80.69%, respectively, the reducing power and DPPH radical scavenging rate experienced a decreasing tendency, but the highest DPPH radical scavenging rate remained at 74.74%. All of these suggested that Tibetan propolis had high antioxidant activity. During in vitro digestion, antioxidant indicators significantly changed, but the changing trend of each indicator was inconsistent. Several indicators still performed well. Tibetan propolis can be used as a premium natural antioxidant.

A glassy phase with glass transition (GT) was formed in a wide B content range of 12–31 at% for (Co0.75Cr0.125Mo0.125)100-xBx alloys. The appearance of GT at the low metalloid content of 12%B among Co-, Fe- and Ni-based alloys is the first, in contrast to the absence of GT for (Fe0.75Cr0.125Mo0.125)88B12 and (Ni0.75Cr0.125Mo0.125)88B12 alloys. The Co-based 12%B glassy alloy crystallized through unique three stages, i.e., glass (G) → [G + hcp + fcc] → [G + fcc] → [fcc + M23B6]. The appearance of GT is due to the necessity of long-range rearrangement of constituent elements for the simultaneous precipitation of hcp and fcc phases from glassy phase. The glass transition temperature, crystallization temperature, Vickers hardness (Hv) and Young's modulus for the Co-based glassy alloys increase linearly with increasing B content and reach 904 K, 946 K, 1566 and 188 GPa, respectively, at 31%B. The good bending plasticity is retained up to 29%B. The crystallization of the 27–29%B alloy occurs through G → [G + M23B6] → [M23B6 + M2B] and the ultrahigh Hv above 2000 is attained for the metastable [G + M23B6] phase state. The glassy alloy rod with a diameter of 1 mm was prepared for the 27%B alloy and exhibited ultrahigh yield strength of 4700 MPa, plastic strain of 1% and high oxidation resistance up to about 1200 K. The Co-based bulk glassy alloy with simultaneously high strength, ultrahigh hardness and high oxidation resistance, is promising for the future high hardness and heat-resistance materials.

Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds—Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin—derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related SIRT3 expression, and others reduced inflammatory TNFα expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.

Non-line-of-sight (NLOS) errors significantly impact the accuracy of ultra-wideband (UWB) indoor positioning, posing a major barrier to its advancement. This study addresses the challenge of effectively distinguishing line-of-sight (LOS) from NLOS signals to enhance UWB positioning accuracy. Unlike existing research that focuses on optimizing deep learning network structures, our approach emphasizes the optimization of model parameters. We introduce a chaotic map for the initialization of the population and integrate a subtraction-average-based optimizer with a dynamic exploration probability to enhance the Snake Search Algorithm (SSA). This improved SSA optimizes the initial weights and thresholds of backpropagation (BP) neural networks for signal classification. Comparative evaluations with BP, Particle Swarm Optimizer–BP (PSO-BP), and Snake Optimizer–PB (SO-BP) models—performed using three performance metrics—demonstrate that our LTSSO-BP model achieves superior stability and accuracy, with classification accuracy, recall, and F1 score values of 90%, 91.41%, and 90.25%, respectively.

A liquid helium-free cryostat for radio frequency (RF) test of the superconducting cavity is designed and constructed. Gifford-Mcmahon (G-M) cryocoolers are used to provide cooling capacity, and the heat leakage at 4 K is less than 0.02 W. Vertical and horizontal tests of two Nb3Sn cavities are carried out in the cryostat with different surface treatments outside the cavities. Both of the cavities achieve stable continuous wave (CW) operation. A novel treatment, which cold-sprayed a 3.5 mm thick Cu layer onto the outside of the cavity, enables the maintenance of an average temperature of 5.5 K in the cavity at a RF loss of 10 W, implying that the thermal stability and uniformity of the cavity has been significantly improved. Through the synergistic control of four metal film resistors, a cooling rate of 0.06 K/min near 18 K is realized, and the cavity temperature gradient is reduced to 0.17 K/m, which effectively improves the RF performance of the cavity. The maximum Eacc of the cavity reaches 3.42 MV/m, and the Q0 is 1.1 × 109. An electromagnetic–thermal coupling simulation model for the superconducting cavity is established and is in good agreement with the experimental results. The simulation results show that the cavity with a Cu-spraying treatment and the thermal links of 5N Al can satisfy the Eacc of 10 MV/m under conduction cooling.

Multiple sclerosis (MS) is a chronic disease characterized by inflammation and neurodegeneration of the central nervous system. Despite the significant role of oxidative stress in the pathogenesis of MS, its precise molecular mechanisms remain unclear. This study utilized microarray datasets from the GEO database to analyze differentially expressed oxidative-stress-related genes (DE-OSRGs), identifying 101 DE-OSRGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that these genes are primarily involved in oxidative stress and immune responses. Through protein–protein interaction (PPI) network, LASSO regression, and logistic regression analyses, four genes (MMP9, NFKBIA, NFKB1, and SRC) were identified as being closely related to MS. A diagnostic prediction model based on logistic regression demonstrated good predictive power, as shown by the nomogram curve index and DAC results. An immune-cell infiltration analysis using CIBERSORT revealed significant correlations between these genes and immune cell subpopulations. Abnormal oxidative stress and upregulated expression of key genes were observed in the blood and brain tissues of EAE mice. A molecular docking analysis suggested strong binding potentials between the proteins of these genes and several drug molecules, including isoquercitrin, decitabine, benztropine, and curcumin. In conclusion, this study identifies and validates potential diagnostic biomarkers for MS, establishes an effective prediction model, and provides new insights for the early diagnosis and personalized treatment of MS.

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation.

The natural environment in the high-altitude regions of Northwest China is extremely harsh, characterized by numerous salt lakes. The high concentrations of chloride salts, sulfates, and alkali metal ions in these areas can induce alkali–silica reactions (ASRs) in concrete. These reactions generate harmful gel within the concrete, causing expansion and cracking, which significantly impacts the durability of concrete structures. This study investigates the evolution of the mechanical properties in high-performance concrete (HPC) under long-term ASR by incorporating different admixtures and varying the equivalent alkali content. A three-dimensional random aggregate mesoscopic model was used to simulate static compression tests under various operational conditions. Non-destructive testing methods were utilized to determine the expansion rate, internal, and surface damage variables of the concrete. The experimental results indicate that the 10-year expansion rate differs from the 1-year rate by approximately 1%, and under long-term ASR mitigation measures, the internal damage in the HPC is minimal, though the surface damage is more severe. As the equivalent alkali content increases, the compressive strength of the concrete cubes decreases, initially rising before falling by 5–15% over time. The HPC with only air-entraining agent added exhibited better mechanical performance than the HPC with both air-entraining and corrosion inhibitors added, with the poorest performance observed in the HPC with only a corrosion inhibitor. A relationship was established between the surface and internal damage variables, with the surface damage initially increasing rapidly before stabilizing as the internal damage rose. Numerical simulations effectively describe the damage behavior of HPC under static uniaxial compression. Comparisons with actual failure morphologies revealed that, in the cube compression tests, crack propagation directly penetrated both coarse and fine aggregates rather than circumventing them. The simulations closely matched the experimental outcomes, demonstrating their accuracy in modeling experiments. This study discusses the compressive mechanical properties of concrete under prolonged ASR through a combination of experimental and simulation approaches. It also delves into the impact of surface damage on the overall mechanical performance and failure modes of concrete. The findings provide experimental and simulation support for the concrete structures in regions with high alkali contents.

One of the effective ways to crack the “Three Rural Issues” and promote rural revitalization is to improve agricultural labor productivity (ALP). However, at this stage, improving China’s ALP is still facing many obstacles and bottlenecks. Promoting migrant workers returning home for entrepreneurship is an important breakthrough point for solving this problem. This paper regards the pilot policy of migrant workers returning home for entrepreneurship as a quasi-natural experiment and empirically investigates the influence of migrant workers returning home for entrepreneurship on ALP and explores its potential mechanism and heterogeneity using county area panel data from 2011–2019. It found the following: Firstly, the policy of migrant workers returning home for entrepreneurship significantly increases ALP. Secondly, migrant workers returning home for entrepreneurship indirectly leads to a rise in ALP through the promotion of agricultural mechanization production. Thirdly, the heterogeneity test demonstrates that migrant workers returning home for entrepreneurship purposes have a significant influence in enhancing ALP in the eastern areas, plains areas and non-agricultural strong areas. The findings of this paper not only provide an important real-world basis for the government to further support migrant workers returning home for entrepreneurship but also provide useful policy insights for the modernization and development of agriculture and rural areas.

Ischemic stroke is a common cerebrovascular disease with high mortality, high morbidity, and high disability. Cerebral ischemia/reperfusion injury seriously affects the quality of life of patients. Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid compound extracted from Ixeris sonchifolia (Bge.) Hance, a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the protective effect of LGU on cerebral ischemia/reperfusion injury was investigated in an oxygen–glucose deprivation/reoxygenation (OGD/R) neuronal model and a transient middle cerebral artery occlusion (tMCAO) rat model. In in vitro experiments, LGU was found to improve the OGD/R-induced decrease in neuronal viability effectively by the MTT assay. In in vivo experiments, neurological deficit scores, infarction volume rates, and brain water content rates were improved after a single intravenous administration of LGU. These findings suggest that LGU has significant protective effects on cerebral ischemia/reperfusion injury in vitro and in vivo. To further explore the potential mechanism of LGU on cerebral ischemia/reperfusion injury, we performed a series of tests. The results showed that a single administration of LGU decreased the content of EB and S100B and ameliorated the abnormal expression of tight junction proteins ZO-1 and occludin and metalloproteinase MMP-9 in the ischemic cerebral cortex of the tMCAO 24-h injury model. In addition, LGU also improved the tight junction structure between endothelial cells and the degree of basement membrane degradation and reduced the content of TNF-α and IL-1β in the brain tissue. Thereby, LGU attenuated cerebral ischemia/reperfusion injury by improving the permeability of the blood–brain barrier. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

The prevalence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasing, with a tendency for co-occurrence. Some studies indicate a connection between atypical sensory processing and executive function. This study aims to explore the distinctive etiology of executive function deficits in children with ASD+ADHD by investigating the relationship between sensory processing and executive function, comparing children with ASD, ASD+ADHD, ADHD, and typically developing children (TD). Method: Sensory Profile 2 (SP-2) and Behavior Rating Inventory of Executive Function 2 (BRIEF-2) were measured in 120 school-aged children. The results of the above scales were compared across these four groups, and correlation and regression analyses between BRIEF2 and SP2 were conducted. Results: Our research revealed varying levels of atypical sensory processing and executive function anomalies across the three neurodevelopmental disorder groups compared to the TD group. The ASD+ADHD group showed particularly significant differences. The heightened emotional problems observed in ASD+ADHD children may be associated with more prominent atypical sensory processing. Variance analysis of inhibitory function revealed differences between ASD+ADHD and ADHD children, suggesting distinct etiological mechanisms for attention issues between ASD+ADHD and ADHD. Conclusions: ASD+ADHD represents a phenotype distinct from both ASD and ADHD. Special consideration should be given to interventions for children with ASD+ADHD. The results of this study may offer a new perspective on understanding the occurrence of ASD+ADHD and potential individualized intervention methods.

In regions characterized by the challenging combination of brine corrosion in the salt lakes and river sand with alkali silica reaction (ASR) activity in areas of the Northwest, high-performance concrete (HPC) formulated with high-volume composite mineral admixtures as ASR suppression measures has been preferred for civil engineering structures in the region. This study investigates the splitting tensile strength, corrosion products, microscopic structure characteristics, and mesoscopic mechanical mechanisms of splitting failure of such HPC under 10-year corrosion from salt lake brine. The relationship between mechanical properties and corrosion damage, as well as the characteristics of internal crack propagation paths and failure mechanisms of HPC under splitting load, are explored. The findings reveal that as the alkali content within HPC rises, corrosion damage intensifies, resulting in a reduction in splitting tensile strength. Moreover, a linear association between mechanical properties and corrosion damage is observed. Microscopic structural analysis and numerical simulation of the splitting failure process of HPC elucidate that while the substantial presence of mineral admixtures effectively suppresses the ASR risk associated with alkali-reactive aggregates in concrete, uneven ASR gel products persist. These discontinuous micro-fine interface cracks induced by the gel products and the cracks induced by the gel products around the selective alkali-active aggregate particles distributed in the local area are the initiation sources of mortar cracks in HPC splitting failure. In terms of the overall failure state observed during the concrete splitting process, mortar cracks manifest two distinct extension paths: along the coarse aggregate interface and directly through the aggregates themselves. Notably, a greater proportion of coarse aggregates are directly penetrated by mortar cracks, as opposed to the number of interface failures bypassing coarse aggregates. More importantly, the above work establishes a theoretical reference in three dimensions: macroscopic, mesoscopic, and microscopic, for studying concrete corrosion damage in complex environments such as salt lake brine corrosion and ASR inhibition.

As a key component of deep-sea manned submersibles, the observation window is usually constructed with polymethyl methacrylate (PMMA) material. During the design of the observation windows, the consideration of actual lifespan and its influential factors is insufficient. There are no clear provisions in the widely applied specifications. In this paper, based on the continuum damage mechanics model, combined with the viscoelastic relationship of PMMA material, a series of calculations were performed on the PMMA observation window. The parametric analysis of the fatigue crack-initiation life of the observation window at various thickness-to-diameter ratios (1.6, 1.4, 1.2, and 1.0), different friction coefficients (0.1, 0.2, and 0.3), and different transition arc radii (4000 mm and 6000 mm) was carried out. The calculated crack positions in the numerical mode used for validation closely align with those in the tested window. And simulation results show that the fatigue life of the observation window gradually decreases with the decrease in the thickness–diameter ratio and the increase in the friction coefficient. However, the increase in the transition arc radius will prolong the fatigue life of the observation window, which is higher than that of the original structure.

Objective To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI).Methods A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters.Results IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91).Conclusion The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

Abstract This study validates a novel structural reliability method, particularly suitable for high‐dimensional green energy harvesting device dynamic systems, versus a well‐established bivariate statistical method, known to accurately predict two‐dimensional system extreme response contours. Classic reliability methods dealing with time series do not always have an advantage of dealing easily with dynamic system high dimensionality, along with complex cross‐correlations among different system components. Energy harvesters constitute an important part of modern offshore green energy engineering; hence, proper experimental study along with safety and reliability analysis are of practical design and engineering importance. To study the performance of galloping energy harvesters, a series of laboratory wind tunnel tests have been conducted, selecting different wind speeds. This study illustrates the usage of the advocated novel reliability method, by analyzing bivariate statistics of experimental galloping energy harvester's dynamics. The bivariate statistics was extracted from available experimental results, more specifically for the device's voltage‐force dataset. Advantage of the proposed methodology being that relatively short experimental data record may still yield meaningful design results, provided proper statistical methods have been applied. Safety and reliability are important engineering concerns for all kinds of green energy devices. In the case of measured device's structural response, an accurate prediction of system failure or damage probability is possible, as illustrated in this study. Distinctive advantage of advocated novel semi‐analytical reliability methodology being the fact that it can tackle dynamic systems with practically unlimited number of dimensions (or components), along with complex nonlinear cross‐correlations between different system key components.

ObjectivesTo review and synthesize qualitative research exploring patients’ safe experience and construct a model to present barriers and facilitators to feeling safe for inpatients.DesignA qualitative met-synthesis.MethodsWe conducted a systematic electronic search of articles published in English with no date limitation across five databases (Ovid MEDLINE, EMBASE, Web of Science, CINAIL via EBSCO, and PsyINFO) in May 2023. Qualitative research focused on the safe experiences of inpatients was considered. Systematic searches yielded 8,132 studies, of which 16 articles were included. Two reviewers independently extracted and analyzed data. Qualitative meta-synthesis was performed through line-by-line coding of original texts, organizing codes into descriptive themes, and generating analytical themes.ResultsWe identified four themes and 11 sub-themes. Across the four themes, control included a barrier (Uncertainty) and two facilitators (Patient participation and safe care); responsible included three facilitators (Confidence in the profession, care for, and responsive); dignity included two barriers (Privacy and Neglect); stability included a barrier (Potential risk), and two facilitators (Harmonious and safe culture). We constructed a model to present the logical connection between these themes and related barriers and facilitators.ConclusionFeeling safe for inpatients is a complex perception, including four themes: control, responsible, dignity, and stability. Surrounding four themes and related barriers and facilitators, we outline principles for creating a safe environment and present strategies for improving patients’ hospitalization experience and ensuring patient safety.Clinical relevanceThis review provides valuable insight into the clinical practice and health policy and helps medical staff to identify and overcome the potential barriers to implementing interventions in safe care. In addition, the model comprehensively describes the nature and dimensions of feeling safe, informing high-quality care service and related research.Systematic review registrationIdentifier, CRD42023435489.

Radiation therapy (RT) not only can directly kill tumor cells by causing DNA double-strand break, but also exerts anti-tumor effects through modulating local and systemic immune responses. The immunomodulatory effects of RT are generally considered as a double-edged sword. On the one hand, RT effectively enhances the immunogenicity of tumor cells, triggers type I interferon response, induces immunogenic cell death to activate immune cell function, increases the release of proinflammatory factors, and reshapes the tumor immune microenvironment, thereby positively promoting anti-tumor immune responses. On the other hand, RT stimulates tumor cells to express immunosuppressive cytokines, upregulates the function of inhibitory immune cells, leads to lymphocytopenia and depletion of immune effector cells, and thus negatively suppresses immune responses. Nonetheless, it is notable that RT has promising abscopal effects and may achieve potent synergistic effects, especially when combined with immunotherapy in the daily clinical practice. This systematic review will provide a comprehensive profile of the latest research progress with respect to the immunomodulatory effects of RT, as well as the abscopal effect of radioimmunotherapy combinations, from the perspective of biological basis and clinical practice.

The maize starch (MS)-stearic acid (SA) and MS-SA-whey protein (WP) complexes were prepared using the high-pressure homogenization (HPH). Results from X-ray diffraction (XRD) showed that MS-SA complexes presented an increase in the long-range molecular order with increasing the homogenization pressure, and MS-SA-WP complexes showed only an increase with increasing the homogenization pressure from 10 to 50 MPa. Results from differential scanning calorimetry (DSC) and Raman spectroscopy showed that the amount of complexes and the short-range order of both MS-SA and MS-SA-WP complexes increased with increasing the homogenization pressure. The addition of WP to MS-SA altered significantly the structure and digestion of complexes. Results revealed that MS-SA-WP complexes have more ordered structure and lower digestion than the corresponding MS-SA complexes. The digestibility of all complexes decreased with increasing the homogenization pressure. There was a significant correlation between the digestibility and structural characteristics of complexes. Complexes with better structural stability have better anti-digestion properties. The obtained results are helpful in understanding the structure and digestibility of complexes prepared by HPH, which is valuable for controlling the quality and nutrition of starchy food.

PurposeThis mini-review delves into the realm of Langerhans cell histiocytosis (LCH) in children, focusing on its skeletal involvement. By synthesizing pertinent literature, we sought to provide a comprehensive understanding of LCH’s clinical and radiographic spectrum. Our study then demonstrates the diagnostic prowess of whole-body 99mTc-methyl diphosphonate (MDP) scintigraphy in LCH cases, underscoring its value in tandem with existing knowledge.MethodsOur approach involved an extensive literature review that contextualized LCH within the current medical landscape. Subsequently, we presented a case series featuring five pediatric instances of skeletal LCH, one accompanied by soft tissue infiltration. The principal aim was to illuminate the diagnostic and staging potential of whole-body 99mTc-MDP scintigraphy, augmenting existing insights.ResultsThrough meticulous literature synthesis, we highlighted pediatric LCH’s protean clinical manifestations and radiological variability. Aligning with this spectrum, our case series underscored the role of 99mTc-MDP scintigraphy in diagnosing and staging LCH. Among the five pediatric cases, one demonstrated concurrent soft tissue involvement. This aligns with the multifaceted nature of LCH presentations.ConclusionPediatric LCH can present with a wide range of clinical and radiologic features. By amalgamating our cases with extant literature, we stress the necessity of a multimodal strategy. 99mTc-MDP scintigraphy emerged as an indispensable tool for accurate staging and soft tissue detection. Our findings collectively advocate for a holistic approach to managing LCH, ensuring informed therapeutic decisions for optimal patient outcomes.

BackgroundIn breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy.MethodsWe collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay.ResultsAmong our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes.ConclusionDifferent breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

IntroductionRecurrent reproductive failure (RRF) is a common pregnancy complication, imposing great physical, emotional and financial burden for the suffered couples. The leading cause of RRF is believed to be aneuploid embryo, which could be solved by preimplantation genetic testing for aneuploidy (PGT-A) in theory. With molecular genetic development, PGT-A based on comprehensive chromosomal screening (CCS) procedures and blastocyst biopsy is widely applied in clinical practice. However, its effects in RRF were not defined yet.MethodsA systematic bibliographical search was conducted without temporal limits up to June, 2023. Studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included.ResultsTwenty studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. It revealed that PGT-A could optimise the reproductive outcomes of RRF sufferers, especially in those with advanced age. However, in patients with multiple occurrences of pregnancy losses, the benefits of PGT-A were limited.DiscussionMore randomized controlled trials with large sample size are required to evaluate the benefits of PGT-A in RRF sufferers and identify which population would benefit the most.

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

HER2 overexpression/amplification is a prevalent driver in various types of cancer, including gastric cancer (GC). Limited options are available for patients with HER2-positive metastatic gastric cancer, particularly those who do not respond to the standard therapy of HER2 antibody trastuzumab combined with chemotherapy. Previous research suggests that combining a PD-1 inhibitor with radiotherapy and granulocyte macrophage-colony stimulating factor (PRaG regimen) may enhance the antitumor effects in patients with chemotherapy-resistant metastatic solid tumors. In this case study, we presented a potential treatment strategy of a patient having HER2-positive and PD-L1-negative gastric adenocarcinoma. The patient showed rapid tumor progression even after surgery and multiple trastuzumab plus chemotherapy treatments. To address this, we employed a novel anti-HER2 antibody called RC48 in combination with PRaG regimen therapy (PRaG3.0). The patient demonstrated a positive response after two treatment cycles and achieved a progression-free survival time of 6.5 months. This case highlights the potential of four-combination therapies for treating refractory, multiorgan, HER2-positive, PD-L1-negative metastatic gastric cancer. Additionally, varying radiation doses in targeting dual foci is critical to enhance tumor immunotherapy.

Diarylheptanoids, potential therapeutic agents and dietary supplements, are the main active compounds in the genus Curcuma, however, determination of the absolute configurations of the flexible polyhydric main chains in linear diarylheptanoids is still a challenge. In this study, an exploration of the phytochemical constituents of Curcuma phaeocaulis led to the isolation of eight novel linear diarylheptanoids (1–8). Enzymatic hydrolysis, preparation of acetonide derivatives, preparation of MTPA esters, and electronic circular dichroism calculations were comprehensively performed in order to determine their absolute configurations. In in vitro assays, compounds 2, 3, and 6 exhibited anti-angiogenic activities, and compounds 2, 3, and their aglycones inhibited the proliferation of HepG2 cells. These findings suggest that diarylheptanoid glucosides of C. phaeocaulis may be useful for suppression of hepatoma growth and metastasis.

ObjectiveSelf-management is crucial in managing recurrent pregnancy loss (RPL). This study explored the knowledge, attitudes, and practices (KAP) of patients with RPL toward RPL.MethodsThis cross-sectional study was conducted among patients with RPL between January 2023 and June 2023 at the Second Hospital of Lanzhou University. Participants’ demographic characteristics and KAP were determined using a self-designed questionnaire (Cronbach’s α = 0.818). Structural equation modeling (SEM) was used to observe the correlations among KAP and different factors.ResultsThis study analyzed 497 valid questionnaires. The mean knowledge, attitude, and practice scores were 11.59 ± 4.30 (possible range: 0–20, 57.95%), 44.17 ± 3.18 (possible range: 13–65, 67.95%), and 32.39 ± 5.22 (possible range: 8–40, 80.98%), indicating poor knowledge, moderate attitude, and proactive practice. Age was non-linearly associated with the KAP dimensions, with a positive impact of age on KAP among those aged

The boundary element method is widely used in practical engineering problems, especially in the field of acoustics. For flow-induced noise, the main target of acoustic calculations is to solve the wave equation with the flow field information. However, the sound field distribution of noncompact structures in half-space is especially complex because of the strong scattering effect, while the object surface boundary integration often brings a large workload and generates numerical singularities. In this paper, an improved boundary element method for predicting the aeroacoustic noise of noncompact structures is proposed, which can consider the characteristic distribution of sound field induced by complex structures in half-space. The smooth permeable boundary surrounding the object is used as the integration boundary, while the scattering effect of the ground boundary is investigated by combining the mirror Green’s function method, and the numerical prediction of aeroacoustic noise is carried out for the dipole source and NACA0012 airfoil in half-space. Numerical results show that the far-field noise obtained by using the permeable surface is consistent with that obtained by integrating the direct object boundary under the influence of ground boundary scattering. The mirror image Green’s function method is able to finely capture the ground scattering effect, which has a significant effect on the sound field as the frequency increases.

It is becoming increasingly clear that maintaining the equilibrium of gut microbiota homeostasis during viral infections, such as Hantaan virus (HTNV), is of paramount importance. In order to gain insight into the role of NOD-like receptors in the immune system, we conducted a comparative study between C57BL/6 and Nlrx1-/- mouse models to analyze changes in the gut microbiota after HTNV infection. Our findings revealed an increase in the ratio of Firmicutes to Bacteroides in Nlrx1-/- mice, suggesting a potential link to inflammation. In addition, a comprehensive analysis of serum metabolomics revealed that differential metabolites were mainly concentrated in amino acid metabolism and lipid metabolism. Amino acid metabolism mainly involves arginine, lysine, and histidine metabolism, while lipid metabolism is mainly related to glycerophospholipid metabolism and fatty acid synthesis. Analysis of the correlation between microbiota and metabolites revealed an inverse relationship between Bacteroidetes and metabolites related to glutamine metabolism, while Firmicutes were directly associated with these metabolites. Furthermore, we observed a negative correlation between the presence of Actinobacteria, Proteobacteria, and Patescibacteria and the metabolites related to polyunsaturated fatty acids (PUFAs). Our results demonstrate that HTNV infection causes changes in the composition of gut microbiota in both Nlrx1-/- and wild-type (WT) mice. Moreover, the fecal microbiota and serum metabolites of Nlrx1-/- mice display notable differences at various developmental stages. Investigating this further may help to improve our understanding of the pathogenesis of HTNV and provide potential therapeutic options.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a “multiple vectors in one AAV” strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp. Under the control of these 2 promoters, green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs. The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system. Driven by these 2 promoters, human otoferlin was selectively expressed in HCs, resulting in the restoration of hearing in treated Otof −/− mice for at least 52 weeks. In summary, we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.

Background and purposeStroke may cause extensive after-effects such as motor function impairments and disorder of consciousness (DoC). Detecting these after-effects of stroke and monitoring their changes are challenging jobs currently undertaken via traditional clinical examinations. These behavioural examinations often take a great deal of manpower and time, thus consuming significant resources. Computer-aided examinations of the electroencephalogram (EEG) microstates derived from bedside EEG monitoring may provide an alternative way to assist medical practitioners in a quick assessment of the after-effects of stroke.MethodsIn this study, we designed a framework to extract microstate maps and calculate their statistical parameters to input to classifiers to identify DoC in ischemic stroke patients automatically. As the dataset is imbalanced with the minority of patients being DoC, an ensemble of support vector machines (EOSVM) is designed to solve the problem that classifiers always tend to be the majority classes in the classification on an imbalanced dataset.ResultsThe experimental results show EOSVM get better performance (with accuracy and F1-Score both higher than 89%), improving sensitivity the most, from lower than 60% (SVM and AdaBoost) to higher than 80%. This highlighted the usefulness of the EOSVM-aided DoC detection based on microstates parameters.ConclusionTherefore, the classifier EOSVM classification based on features of EEG microstates is helpful to medical practitioners in DoC detection with saved resources that would otherwise be consumed in traditional clinic checks.

This study, conducted in China in November 2020, was aimed at exploring the variations in growth traits among different provenances and families as well as to select elite materials of Juglans mandshurica. Thus, seeds of 44 families from six J. mandshurica provenances in Heilongjiang and Jilin provinces were sown in the nursery and then transplanted out in the field. At the age of 5 years, seven growth traits were assessed, and a comprehensive analysis was conducted as well as selection of provenance and families. Analysis of variance revealed statistically significant (P < 0.01) differences in seven growth traits among different provenances and families, thereby justifying the pursuit of further breeding endeavors. The genetic coefficient of variation (GCV) for all traits ranged from 5.44% (branch angle) to 21.95% (tree height) whereas the phenotypic coefficient of variation (PCV) ranged from 13.74% (tapering) to 38.50% (branch number per node), indicating considerable variability across the traits. Further, all the studied traits except stem straightness degree, branch angle and branch number per node, showed high heritability (Tree height, ground diameter, mean crown width and tapering, over 0.7±0.073), indicating that the variation in these traits is primarily driven by genetic factors. Correlation analysis revealed a strong positive correlation (r > 0.8) between tree height and ground diameter (r = 0.86), tree height and mean crown width (r = 0.82), and ground diameter and mean crown width (r = 0.83). This suggests that these relationships can be employed for more precise predictions of the growth and morphological characteristics of trees, as well as the selection of superior materials. There was a strong correlation between temperature factors and growth traits. Based on the comprehensive scores in this study, Sanchazi was selected as elite provenance. Using the top-percentile selection criteria, SC1, SC8, DJC15, and DQ18 were selected as elite families. These selected families exhibit genetic gains of over 10% in tree height, ground diameter and mean crown width, signifying their significant potential in forestry for enhancing timber production and reducing production cycles, thereby contributing to sustainable forest management. In this study, the growth traits of J. mandshurica were found to exhibit stable variation, and there were correlations between these traits. The selected elite provenance and families of J. mandshurica showed faster growth, which is advantageous for the subsequent breeding and promotion of improved J. mandshurica varieties.

Traditional Chinese medicine volatile oil has a long history and possesses extensive pharmacological activity. However, volatile oils have characteristics such as strong volatility, poor water solubility, low bioavailability, and poor targeting, which limit their application. The use of volatile oil nano drug delivery systems can effectively improve the drawbacks of volatile oils, enhance their bioavailability and chemical stability, and reduce their volatility and toxicity. This article first introduces the limitations of the components of traditional Chinese medicine volatile oils, discusses the main classifications and latest developments of volatile oil nano formulations, and briefly describes the preparation methods of traditional Chinese medicine volatile oil nano formulations. Secondly, the limitations of nano formulation technology are discussed, along with future challenges and prospects. A deeper understanding of the role of nanotechnology in traditional Chinese medicine volatile oils will contribute to the modernization of volatile oils and broaden their application value.

ObjectiveThis study investigated how anticipated instrumental support sources and intergenerational support influence depressive symptoms in older Chinese adults.MethodsWe employed binary logistic regression on data from 7,117 adults aged ≥60 in the 2018 China Health and Retirement Longitudinal Study, controlling for gender, marital status, and self-rated health.Results38.89% of respondents exhibited depressive symptoms. Anticipated support from spouse and children, spouse only, children only, or other sources showed 52, 25, 46, and 40% lower odds of depression, respectively, compared with no anticipated support. Those providing financial support had 36% higher odds of depression than those without exchanges. However, those receiving financial support, receiving instrumental support, and receiving and providing financial and emotional support had 19, 14, 23, and 24% lower odds of depression.ConclusionDifferent anticipated instrumental support sources and intergenerational support influenced depression odds in older adults, suggesting potential benefits in promoting such support systems.

The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing.