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Min Fang,1,2 Wei Yin,3 Chunyan Qiu,4 Tao Song,2 Baihua Lin,2 Ying Wang,2 Hanchu Xiong,2 Shixiu Wu1 1Department of Radiation Oncology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Wei Yin, Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China, Email hzyinwei@live.cn Shixiu Wu, Department of Radiation Oncology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email wushixiu@yeah.netObjective: Immune cells play a key role in tumor microenvironment. The purpose of this study was to investigate the infiltration and clinical indication of immune cells including their combined prognostic value in microenvironment of triple negative breast cancer.Methods: We investigated 100 patients with triple negative breast cancer by Opal/Tyramide Signal Amplification multispectral immunofluorescence between 2003 and 2017 at Zhejiang Provincial people’s Hospital. Intratumoral and stromal immune cells of triple negative breast cancer were classified and quantitatively analyzed. Survival outcomes were compared using the Kaplan–Meier method and further analyzed with multivariate analysis.Results: Infiltration level of stromal B lymphocytes, stromal and intratumoral CD8+ T cells, stromal CD4+ T cells, stromal PD-L1 and intratumoral tumor associated macrophages 2 cells were shown as independent factors affecting disease-free survival and overall survival in univariate analysis. Stromal B lymphocytes, T stage, N stage and pathological type were independent predictive factors for both DFS and OS in multivariate analysis. We firstly found that patients with B lymphocytes-enriched subtypes have a better prognosis than those with T lymphocytes-enriched subtypes and tumor-associated macrophage-enriched subtypes.Conclusion: The present study identified a bunch of immune targets and subtypes, which could be exploited in future combined immunotherapy/chemotherapy strategies for triple negative breast cancer patients.Keywords: triple negative breast cancer, B lymphocytes, T lymphocytes, tumor associated macrophages, multispectral immunofluorescence, prognosis

Xue Zhang,1,* Aili Zhang,2,* Hao Guan,1 Li Zhou,1 Jiao Zhang,3 Wenjie Yin1 1Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 2Department of Scientific Research, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 3Department of Basic Medicine, Zhaotong Health Vocational College, Zhaotong, Yunnan, 657000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjie Yin; Xue Zhang, Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China, Email yinwenjie0606@163.com; zxyougubaihe@163.comObjective: Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months.Methods: Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded.Results: Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend.Conclusion: This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.Keywords: platelet-rich plasma, chronic low back pain, meta-analysis, randomized controlled trial, clinical efficacy

OBJECTIVE: To investigate the effects of parecoxib on postoperative cognitive dysfunction, and serum levels of neuron-specific enolase (NSE) and S100β protein (S100β) in elderly patients undergoing surgery. PATIENTS AND METHODS: The retrospective cohort study method was used to collect the clinical data of 94 elderly patients who underwent elective orthopedic and general anesthesia surgery in our hospital from September 2020 to February 2022. 94 patients were divided into the control group (47 cases) and the study group (47 cases), according to different intervention methods. In the study group, 40 mg of parecoxib was injected intravenously into patients 30 min before the induction of anesthesia, and the patients in the control group were given the same dose of normal saline intravenously before the operation. The basic clinical data of the patients were collected. The levels of the indexes before operation and 6 hours after operation were compared between the two groups, including the Montreal Cognitive Scale (MoCA) score, inflammatory factor indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), monocyte chemokine-1 (MCP-1), and inducible nitric oxide synthase (iNOS)], serum cortisol (CORT), beta-amyloid (β-AP), adiponectin (ADP), NSE, and S100β. RESULTS: No significant differences in the preoperative MoCA score, TNF-α, IL-6, CRP, IL-10, IL-1β, MCP-1, iNOS, CORT, β-AP, ADP, NSE, and S100β levels were observed between the two groups (p>0.05). The postoperative MoCA score in the study group was significantly higher than that in the control group (p<0.05). The postoperative levels of TNF-α, IL-6, CRP and IL-1β in the study group were significantly lower than those in the control group (p<0.05), and the postoperative levels of IL-10, MCP-1 and iNOS in the study group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: Parecoxib can notably inhibit the levels of postoperative inflammatory cytokines, improve neurological dysfunction, and reduce the occurrence of postoperative cognitive dysfunction in patients. The contents of serum NSE and S100β have potential value in the diagnosis of postoperative cognitive dysfunction in elderly patients. [ABSTRACT FROM AUTHOR]

Abstract Optical wireless communication (OWC) stands out as one of the most promising technologies in the sixth-generation (6G) mobile networks. The establishment of high-quality optical links between transmitters and receivers plays a crucial role in OWC performances. Here, by a compact beam splitter composed of a metasurface and a fiber array, we proposed a wide-angle (~120°) OWC optical link scheme that can parallelly support up to 144 communication users. Utilizing high-speed optical module sources and wavelength division multiplexing technique, we demonstrated each user can achieve a communication speed of 200 Gbps which enables the entire system to support ultra-high communication capacity exceeding 28 Tbps. Furthermore, utilizing the metasurface polarization multiplexing, we implemented a full range wide-angle OWC without blind area nor crosstalk among users. Our OWC scheme simultaneously possesses the advantages of high-speed, wide communication area and multi-user parallel communications, paving the way for revolutionary high-performance OWC in the future.

In this study, three types of three-layer functionally graded materials (FGMs) were designed by mainting the average content of the reinforcement constant and changing the span of the composition. The B4C particle-reinforced Al-matrix FGMs and a homogeneous composite (HC) with the same average composition were prepared using the laser additive manufacturing technique. The FGMs had a higher average secondary-phase content and grain size than the HC. Large (black) and reticulated (white) secondary phases corresponding to B4C phase, T phase, and MgZn2 were observed in the as-deposited FGM samples. The content of the secondary phase in the middle layer was generally low. The bottom layer, which was in direct contact with the substrate, exhibited the smallest grain size. The hardness and wear resistance significantly improved owing to the high B4C content in the top layer. The flexural behaviors of each layer of the FGM in different directions were systematically studied. The plasticity of the single-layer material decreased with increase in the B4C content. When the bottom layer had a high B4C content, the flexural ability significantly reduced. Among all the samples, G2 with 8% B4C particle content in the top layer exhibited the best comprehensive mechanical properties. The hardness value, wear rate of the top layer, maximum bending stress, and maximum bending strain of the FGM were 177.5 HV, 0.367 × 10−3mm3/(N·m), 585.6 MPa, and 7.36%, respectively. This study can provide a reference value for the future design and development of wear-resistant gradient materials for aerospace applications.

Three types of 7185+TiB2/TiC aluminum matrix composites with different Zn/Mg ratios were prepared in this work through a water-cooled copper casting process. The effects of Zn/Mg ratio on the microstructure and mechanical properties of 20-mm-thick composites were studied by optical microscopy, electron back scattering diffraction, transmission electron microscopy, and tensile mechanical testing. The results showed that the addition of appropriate TiB2/TiC particles refined the as-cast microstructure of the alloy, and with a decrease in Zn/Mg ratio, the grain size distribution became more uniform, the crystalline phase content gradually increased, and the uniformity of the alloy increased. After aging, as the Zn/Mg ratio decreased, the size of the precipitated phase decreased, and the strengthening effect of the alloy improved. The tensile strengths of the surface layer, 1/4 layer, and center position of the A3 alloy were 558, 568, and 572 MPa, respectively. The strength difference among the different thickness layers was the smallest, and the elongation rate was greater than 12%, resulting in the best uniformity.

To promote adsorption capacity of biochar as engineering material, pinewood biochar (PC) and bamboo biochar (BC) were prepared by slow pyrolysis (700 °C) and then directly irradiated with UV light at room temperature. The elemental analysis, SEM, FTIR, XPS, and Boehm titration measurements showed that UV irradiation significantly increased the BET surface area, porosity, and surface oxygen functional groups of the biochar. After UV treatment, the BET surface areas of PC and BC were increased by 63.0% and 217%, while the amount of total (acidic) groups increased by 62.0% (155%) and 24.9% (28.2%), respectively. FTIR and XPS measurements suggested that photochemical reactions, including photodegradation and photooxidation processes, may play primary roles in altering biochar the pore structure and surface functional groups of biochar. The Langmuir model capacities (qmax) of modified PC and BC were increased by 94.5% and 50.5% for Pb (II), 18.5% and 13.7% for Cd (II), respectively, compared to their unmodified counterparts. This study examined the effects of UV irradiation on the surface properties of biochar and demonstrate its potential as an effective, simple, and green method for functionalizing biomass material.

Abstract Low-dimensional multiferroics, which simultaneously possess at least two primary ferroic order parameters, hold great promise for post-Moore electronic devices. However, intrinsic one-dimensional (1D) multiferroics with the coexistence of ferroelectricity and ferromagnetism are still yet to be realized, which will be not only crucial for exploring the interplay between low-dimensionality and ferroelectric/ferromagnetic ordering but also significant in rendering application approaches for high density information technologies. Here, we present a theoretical prediction of intrinsic multiferroicity in 1D molybdenum oxytrihalides nanowires, especially focusing on MoOBr3 nanowires which could be readily extracted from experimentally synthesized van der Waals MoOBr3 bulk materials. Due to the spatial inversion symmetry spontaneously broken by Mo atoms’ displacements, MoOBr3 nanowires exhibit 1D ferroelectricity with small coercive electric field and exceptional Curie temperature (~570 K). Additionally, MoOBr3 nanowires also possess 1D antiferroelectric metastable states. On the other hand, both ferroelectric and antiferroelectric MoOBr3 nanowires exhibit ferromagnetic ordering on account of the half-filled Mo-d yz orbitals, a moderate tensile strain (~5%) can greatly boost the spontaneous polarization (~40%) and a mild compress strain (~−2%) may readily switch the magnetic easy axis of ferroelectric MoOBr3 nanowires. Our work holds potential candidates for developing innovative devices that exploit intrinsic multiferroic properties, enabling advancements in novel electronic and spintronic applications.

Coal mining engineering involves complex stress structure time effect issues, which are closely related to the occurrence and prevention of rock burst disasters. Therefore, this study conducts experimental research on the stress structure time effect of impact coal. Coal rock specimens were obtained from three coal mines in Shaanxi, Gansu, and Inner Mongolia. The stress-time effect of loading rate was studied through coal uniaxial compression static-dynamic load and creep tests. The stress-time effect under the condition of coal in situ release was investigated using a long-term segmented test method. Water immersion tests on coal and structural time-effect studies on coal-rock combinations were conducted. The experimental results indicate that there is a positive correlation between the uniaxial compressive strength of coal and the loading rate, and a negative correlation with the duration of in-situ relief and immersion time. The combined mode of coal-rock structure time effect significantly affects its energy and strength properties, while impact coal exhibits both stress and structural time effects. According to the experimental results, a plastic limit structure is proposed to explain the irreversible deformation of coal-rock mass under stress. Furthermore, by constructing a time-dependent model for plastic strain in coal under impact conditions and comparing the numerical approximations of non-elastic strain and irreversible strain, the plastic limit strain characteristics of shock-induced coal were verified.

Abstract Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5–41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0–21.5%; difference of 17.6%, 95% CI 11.6–23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of − 0.3% (95% prediction interval − 17.0–16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.

Abstract Background The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported. Results We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria. Extending antibiotic exposure to 2–3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1β (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001). Conclusions Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses,

Background: Pancreatic cysts in autosomal dominant polycystic kidney disease (ADPKD) correlate with PKD2 mutations, which have a different phenotype than PKD1 mutations. However, pancreatic cysts are commonly overlooked by radiologists. Here, we automate the detection of pancreatic cysts on abdominal MRI in ADPKD. Methods: Eight nnU-Net-based segmentation models with 2D or 3D configuration and various loss functions were trained on positive-only or positive-and-negative datasets, comprising axial and coronal T2-weighted MR images from 254 scans on 146 ADPKD patients with pancreatic cysts labeled independently by two radiologists. Model performance was evaluated on test subjects unseen in training, comprising 40 internal, 40 external, and 23 test–retest reproducibility ADPKD patients. Results: Two radiologists agreed on 52% of cysts labeled on training data, and 33%/25% on internal/external test datasets. The 2D model with a loss of combined dice similarity coefficient and cross-entropy trained with the dataset with both positive and negative cases produced an optimal dice score of 0.7 ± 0.5/0.8 ± 0.4 at the voxel level on internal/external validation and was thus used as the best-performing model. In the test–retest, the optimal model showed superior reproducibility (83% agreement between scan A and B) in segmenting pancreatic cysts compared to six expert observers (77% agreement). In the internal/external validation, the optimal model showed high specificity of 94%/100% but limited sensitivity of 20%/24%. Conclusions: Labeling pancreatic cysts on T2 images of the abdomen in patients with ADPKD is challenging, deep learning can help the automated detection of pancreatic cysts, and further image quality improvement is warranted.

Abstract Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.

Objective Aiming at the insufficient control indexes for high-speed railway subgrade horizontal deformation currently, it is necessary to study the influence law and limit values of ballastless track subgrade horizontal deformation. Method Using finite element method, the structural stress, deformation, and track irregularity of CRTS (China railway track system) II type ballastless track are calculated under horizontal deformation conditions of cosine-shaped subgrade with different wavelengths and amplitudes. Referring to the allowable tolerance values for track geometric dimensions and the allowable tensile stress values of ballastless track structure, the transmission law and limit values of subgrade cosine-shaped horizontal deformation are studied. Result & Conclusion The horizontal deformation of ballastless track structures such as rail, track slab, mortar layer and supporting layer shows significant response characteristics to cosine-shaped horizontal deformation of high-speed railway subgrade. When the wavelength and amplitude of horizontal deformation are 20 m and 10 mm respectively, the influence of subgrade cosine-shaped horizontal deformation on track alignment irregularity is the greatest, followed by the influence on track horizontal irregularity, while the influence on gauge and vertical irregularity indicators can be ignored. When the amplitude of horizontal deformation is 20 mm, as its wavelength increases, the maximum value of rail horizontal deformation increases, while the track irregularity, track slab and supporting layer tensile stresses first increase and then decrease. The limit value of subgrade cosine-shaped horizontal deformation amplitude increases with the increase of horizontal deformation wavelength, and the two satisfy a quadratic function relationship.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. Methods The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. Results Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. Conclusions Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People’s Hospital in 2021 (ChiCTR1900024415).

Abstract The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 (origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2, Cyclin B2, and DNA topoisomerase II (TOP2A), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6. RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.

Exploring the impact of elevated CO2 on photosynthesis is vital for understanding plant responses to climate change. In C3 plants, elevated CO2 concentrations generally enhance CO2 assimilation by increasing chloroplast CO2 concentration. However, the underlying mechanisms are complex since photosynthesis involves multiple physiological processes operating at different time scales and varying among plant species. In this review, we focused on the responses of key photosynthetic processes in crop, including CO2 diffusion conductances such as stomatal conductance (gs), mesophyll conductance (gm), photochemical reactions, the Calvin-Benson cycle, and related metabolic pathways. Short-term exposure to elevated CO2 often decreases gs and gm while increasing the electron transport rate. However, long-term exposure to elevated CO2 can decrease photosynthetic capacity due to coordinated downregulation of multiple processes, particularly when the sink‒source ratio declines. To enhance plant productivity under elevated CO2, it is crucial to maintain or enhance sink activity and understand the CO2 response mechanisms at the molecular, physiological, and morphological levels. This review provides an update on the short- and long-term responses of gs, gm, electron transport system, and carbon assimilation metabolism to elevated CO2. Furthermore, it offers a perspective on improving crop production in the future with elevated CO2 levels.

Abstract Background The relationships among left heart remodeling, cardiac function, and cardiovascular events (CEs) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) undergoing maintenance hemodialysis (MHD) remain unclear. We evaluated the echocardiographic characteristics and clinical outcomes of such patients with diverse left ventricular geometric (LVG) configurations. Methods Overall, 210 patients with HFpEF undergoing MHD (cases) and 60 healthy controls were enrolled. Cases were divided into four subgroups based on LVG and were followed up for three years. The primary outcomes were the first CEs and all-cause mortality. Results Left ventricular ejection fraction (LVEF) and right ventricular systolic function did significantly differ between cases and controls, whereas echocardiographic parameters of cardiac structure, diastolic function, and left ventricular global longitudinal strain (LVGLS) differed significantly. The proportion of cases with left ventricular hypertrophy (LVH) was 67.1%. In addition, 2.38%, 21.90%, 12.86%, and 62.86% of cases presented with normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH), respectively. The left atrial diameter (LAD) was the largest and cardiac output index was the lowest in the EH subgroup. The score of Acute Dialysis Quality Initiative Workgroup (ADQI) HF class was worse in the EH subgroup than in other subgroups at baseline. The proportions of cases free of adverse CEs in the EH subgroup at 12, 24, and 36 months were 40.2%, 14.8%, and 0%, respectively, and the survival rates were 85.2%, 29.6%, 3.7%, respectively, which were significantly lower than those in other subgroups. Multivariate Cox regression revealed that age, TNI (Troponin I), EH, left ventricular mass index (LVMI), age and EH configuration were independent risk factors for adverse CEs and all-cause mortality in the cases. Conclusion Most patients with HFpEF receiving MHD have LVH and diastolic dysfunction. Among the four LVGs, patients with HFpEF undergoing MHD who exhibited EH had the highest risk of adverse CEs and all-cause mortality.

With the continuous development and maturity of critical care medicine, the problem of hospital acquired infection(HAI) in the department of critical care medicine has become increasingly prominent. HAI can cause serious adverse consequences, therefore, clarifying its key links and pathogenesis, and exploring more reasonable and effective systematic prevention and control measures are of great significance for reducing HAI in the department of critical care medicine. In addition to systematic prevention and control measures, multidisciplinary collaboration, strong support from administrative departments, and strict implementation of the specific details of HAI prevention and control are also indispensable for properly solving this intractable problem.

In this study, the synergistic effect of Quillaja saponin (QS) and soybean protein isolate (SPI) on stabilizing emulsion gels was used to prepare plant-based mayonnaise (PM) with high protein content and reduced fat content. Comparative characterization of PM and two commercially mayonnaises in terms of appearance, droplet size, texture, rheological properties, thermal and freeze-thaw stability was conducted by static light scattering, laser confocal scanning microscopy (LCSM), small deformation rheology and texture profile analysis (TPA). It was found that high-protein and fat-reduced MP (10% SPI and 50% fat or 11% SPI and 40% fat, m/m) which was compared to commercial mayonnaises in terms of appearance, spreadability, texture and rheological properties was made using 10% SPI and 0.18% QS or 10% SPI, 0.18% QS and 1% SPI gel particles (SGPs) as protein ingredients. In the systems, QS not only endowed a viscosity-thinning texture modifier to protein-rich emulsion products, but also imparted superior thermal stability and freeze-thaw stability to SPI-based emulsion gels. These findings will provide theoretical and technical guidance for the development and application of high-protein and fat-reduced plant-based mayonnaise.

Objective: To provide a synthesis of randomized controlled trials (RCTs) investigating statin-associated muscle symptoms (SAMS) in adults who underwent exercise training intervention. Patients and Methods: We systematically searched 5 electronic databases for placebo-controlled RCTs through January 31, 2023. We included short-term and long-term exercise interventions that compared the efficacy and safety of exercise+statin vs exercise+placebo in healthy adults and reported SAMS preintervention and postintervention. Publication bias and methodological study quality assessments were performed. Results: Five of 454 potentially qualifying RCTs met the inclusion criteria, all short-term exercise RCTs. Participants were predominantly physically inactive young to middle-aged (M=37.2 y) men (57%), 252 (49%) who were on statin therapy, and 271 (53%) on placebo. Of the 3 RCTs providing qualitative SAMS results, 19 (9%) out of 220 participants reported SAMS on exercise+statin and 10 (4%) out of 234 reported SAMS on exercise+placebo. There was no difference between exercise+statin vs exercise+placebo for maximal oxygen consumption (d=−0.18; 95% CI, −0.37 to 0.00; P=.06) or creatine kinase after short-term exercise (d=0.59; 95% CI, −0.06 to 1.25; P=.08). Participants in the exercise+statin group reduced low-density lipoprotein cholesterol vs exercise+placebo (d=−1.84; 95% CI, −2.28 to −1.39; P

IntroductionThis study investigates the dynamic shifts in soil bacterial communities within a Salix matsudana afforested ecosystem transitioning from agricultural land. Understanding the temporal variability in bacterial diversity and community structures is crucial for informing forest management and conservation strategies, particularly in regions undergoing afforestation.MethodsWe employed high-throughput sequencing across three distinct months (August, September, and October) to analyze the temporal variability in bacterial community composition and diversity. Network analysis was utilized to identify keystone species and assess community stability under varying environmental conditions, including fluctuations in temperature and precipitation.ResultsWe uncover significant temporal variability in bacterial diversity and community structures, which are closely tied to fluctuations in temperature and precipitation. Our findings reveal the abundance of the dominant bacterial phyla, such as Actinobacteria and Proteobacteria, which did not change overall, highlighting the stability and resilience of the microbial community across seasonal transitions. Notably, the increasing similarity in community composition from August to October indicates a reduction in species turnover, likely driven by more homogeneous environmental conditions. Through comprehensive network analysis, we identify the pivotal role of keystone species, particularly the human pathogen Nocardia, in maintaining community stability under reduced soil moisture. The observed variations in community connectivity underscore the microbial community’s resilience and adaptability to seasonal shifts, with higher stability in August and October contrasting with the instability observed in September.DiscussionThese results underscore the complex interplay between stochastic and deterministic processes in bacterial community assembly, significantly shaped by prevailing environmental conditions. The insights gained from this research have far-reaching implications for forestry management and conservation strategies, particularly in regions undergoing similar afforestation efforts.

BackgroundPulmonary Artery in situ Thrombosis (PAIST) refers to a thrombus forming within the pulmonary arterial system, distinct from an embolus originating from elsewhere in the body (e.g., the deep veins of the lower extremities) and traveling to the lungs where it lodges and forms.Case presentationWe present a case of PAIST caused by the arterial ductus arteriosus. The patient primarily presented with dyspnea, and the chest pain dichotomy Computed Tomography Angiography(CTA) suggested that a nodular low-density filling defect was seen in the lumen of the left pulmonary artery trunk. Initially, pulmonary embolism (PE) was suspected. However, upon reevaluation of the imaging, it became apparent that the patient's pulmonary artery obstruction was closely associated with the ductus arteriosus. After admission, the patient was treated with sodium ampicillin (2.0 g Q12H) for infection, heparin sodium (5,000 IU Q12H) for anticoagulation, and metoprolol succinate extended-release tablets (23.75 mg QD) to correct cardiac remodeling, among other treatments. Subsequently, the patient underwent a cardiac surgery involving the ligation of the arterial duct, resection of pulmonary artery lesions, and open-heart surgery with extracorporeal circulation support. Postoperative examination of the pulmonary artery mass indicated coagulation tissue. The final diagnosis was “PAIST”.ConclusionBoth PAIST and PE manifest as low-density filling defects in the pulmonary arteries. However, due to the relative unfamiliarity with PAIST, such findings are often initially attributed to PE.

Background: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. Objective: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). Method: This study included 285 mother–child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. Results: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P

Vegetation can reduce the adverse effect of climate change. Under the frequent droughts and global warming, it is critical to clear vegetation dynamics and response to climatic variables. However, it is unclear how drought and climatic variables affect vegetation dynamics. In this study, we used the vegetation condition index (VCI) to examine vegetation dynamics in China between 2001 and 2020. The average annual value of VCI had increased during the period of 2001 to 2020, and 90.63% of the study regions had a rising trend in VCI. A large portion of the area had a 3-month time lag between VCI and temperature and precipitation. The time-lag response of VCI to drought was mainly 9 months, with a cumulative effect on drought of 1 month and 12 months. The VCI of evergreen needleleaf forests (ENF), deciduous needleleaf forests (DNF), deciduous broadleaf forests (DBF), and mixed forests (MF) in northern China displayed long time-lag response to drought. Except for DBF in the north and DNF in the central south regions, the cumulative effect of drought on other forest VCI was great in northern China. Except for DNF, DBF, and MF in the central south and DBF in the southwest regions, drought had less time-lag effects on VCI for ENF, evergreen broadleaf forests (EBF), DNF, and MF in southern China. The cumulative effect of drought on VCI of forests in southern China was short. The responses of various types of the grassland and shrubland to drought were similar as those of forests. However, the time-lag effect of drought on grassland and shrubland VCI was shorter than that of forests, making the grassland and shrubland more vulnerable to the short-term cumulative effects of drought. The result of this study can help us understand how the vegetation responds to climate change and drought under global warming scenarios.

Background and purposeArteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score.Materials and methodsThis is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1–4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz’s method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman’s rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD.ResultsIAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p

The fishery resources in the Yangtze River Estuary (YRE) have declined drastically because of overfishing and environmental changes, leading to ecosystem degradation of the YRE, and bringing numerous rare fish species to the brink of extinction. As a new technology with great prospects for popularization and application, environmental DNA (eDNA) technology has been utilized and proven by many studies to have high potential in revealing the various species' biodiversity. In this study, we analyzed the species composition and diversity of the Yangtze River Estuary using a combination of eDNA technology and bottom trawling approaches, and later, the comparison of both methods. The results showed that combining eDNA technology and bottom trawling, 30 fish species from 7 orders and 11 families were identified. Among the 30 fish species, a total of six species of fish could be observed in catches from both methods. Perciformes were the most abundant and Coilia mystus was the dominant species. According to diversity indices, the eDNA technology reveals significant differences in fish community richness and diversity in the Yangtze River Estuary compared to the bottom trawl. In summary, the eDNA technology is feasible for monitoring fishery resources in the waters of the Yangtze River Estuary, thereby serving as a valuable supplementary tool for conducting comprehensive surveys in this region. Moreover, it holds significant implications and promising prospects for conserving the diverse ecosystem of the YRE in future conservation efforts.

Background: Homer protein homolog 3 (HOMER3), a factor implicated in both physiological and pathological processes, has been studied extensively to determine the relationship between its expression level and the prognosis of various malignancies. However, the significance and clinicopathological role of HOMER3 in colorectal adenocarcinoma remain unclear. Methods: In this study, bioinformatics techniques were used to find the correlation between high HOMER3 expression levels and clinicopathological features of colorectal adenocarcinoma (COAD) patients. Results: Cellular experiments confirmed the differential expression of HOMER3 in tumor cells compared to normal cells. HOMER3 overexpression was significantly associated with COAD staging and carcinoembryonic antigen (CEA) levels. Patients with high HOMER3 expression levels have a poor prognosis. HOMER3 expression levels can be distinguished more accurately between tumor and non-tumor tissues (AUC = 0.634). The HOMER3 gene variation rate in COAD tissue was 0.7 %. Moreover, 16 of the 22 DNA methylation sites in HOMER3 were associated with COAD prognosis. Our findings confirmed that HOMER3 was positively correlated with immune cell infiltration and immune checkpoints (PD-1, CTLA-4, LMTK3, and LAG3) in COAD, Specifically, we will clearly state that while there is statistical significance, the actual strength of the correlations is weak. During KEGG enrichment analysis, HOMER3 was enriched along with DLG4 and SHANK1 in glutamatergic synapses. Additionally, upstream microRNAs that could bind to HOMER3 were predicted. These findings suggest that HOMER3 might be involved in COAD development and immune regulation. Conclusions: HOMER3 acts as a potential biomarker that can facilitate innovative developments in the diagnosis and prognostic assessment of COAD.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

The hydrolysis of MgH2 delivers high hydrogen capacity (15.2 wt%), which is very attractive for real-time hydrogen supply. However, the formation of a surface passivation Mg(OH)2 layer and the large excess of H2O required to ensure complete hydrolysis are two key challenges for the MgH2 hydrolysis systems. Now, a low-cost method is reported to synthesize MgH2@Mg(BH4)2 composite via ball-milling MgH2 with cheap and widely available B2O3 (or B(OH)3). By adding small amounts of B2O3, the in-situ formed Mg(BH4)2 could significantly promote the hydrolysis of MgH2. In particular, the MgH2–10 wt% B2O3 composite releases 1330.7 mL·g−1 H2 (close to 80% theoretical hydrogen generation H2) in H2O and 1520.4 mL·g−1 H2 (about 95%) in 0.5 M MgCl2 in 60 min at 26 °C with hydrolysis rate of 736.9 mL·g−1·min−1 and 960.9 mL·g−1·min−1 H2 during the first minute of the hydrolysis, respectively. In addition, the MgCl2 solution allows repeated use by filtering and exhibits high cycle stability (20 cycles), therefore leading to much reduced capacity loss caused by the excess H2O. We show that by introducing B2O3 and recycling the 0.5 M MgCl2 solution, the system hydrogen capacity can approach 5.9 wt%, providing a promising hydrogen generation scheme to supply hydrogen to the fuel cells.

Abstract With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few of these modifications can lead to base pair changes, which are called RNA editing. RNA editing is a ubiquitous modification in mammalian transcriptomes and is an important co/posttranscriptional modification that plays a crucial role in various cellular processes. There are two main types of RNA editing events: adenosine to inosine (A-to-I) editing, catalyzed by ADARs on double-stranded RNA or ADATs on tRNA, and cytosine to uridine (C-to-U) editing catalyzed by APOBECs. This article provides an overview of the structure, function, and applications of RNA editing enzymes. We discuss the structural characteristics of three RNA editing enzyme families and their catalytic mechanisms in RNA editing. We also explain the biological role of RNA editing, particularly in innate immunity, cancer biogenesis, and antiviral activity. Additionally, this article describes RNA editing tools for manipulating RNA to correct disease-causing mutations, as well as the potential applications of RNA editing enzymes in the field of biotechnology and therapy.

Abstract Background Air pollution poses a significant health risk to the human population, especially for vulnerable groups such as the elderly, potentially discouraging their engagement in physical activity. However, there is a lack of sufficient objective and longitudinal data in current research on how air pollution affects physical activity among older adults. With these gaps, we aimed to explore the relationship between air pollution and objective measurement-based physical activity among older adults by engaging in a longitudinal study design. Methods A total of 184 older adults were recruited from three cities with varying levels of air quality. Mean daily minutes of physical activity were measured with 7 consecutive days of accelerometer monitoring (ActiGraph GT3X-BT). Corresponding air pollution data including daily PM2.5 (µg/m3), PM10 (µg/m3) and air quality index (AQI) were sourced from the China National Environmental Monitoring Centre at monitor locations close to older adults’ addresses. Associations between air quality and physical activity were estimated using a fixed effect model, adjusting for average daytime temperature, rain, age and weight. Results AQI and PM2.5 were observed to exhibit significant, inverse, and linear associations with mean daily walk steps, minutes of light physical activity (LPA), moderate physical activity (MPA) and moderate-to-vigorous physical activity (MVPA) in the single variable models. A one-level increase in AQI corresponded to a decline in 550.04 steps (95% [CI] = -858.97, -241.10; p

In the mammalian heart, cardiomyocytes are forced to withdraw from the cell cycle shortly after birth, limiting the ability of the heart to regenerate and repair. The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal. With the continuous development of genetic lineage tracking technology, it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic, juvenile, and adult stages of cardiogenesis, but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction. It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury, which offers hope for the clinical treatment of myocardial infarction. However, the regeneration frequency and source of cardiomyocytes are still low, and the mechanism of regulating cardiomyocyte proliferation remains further explained. It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration. Here, we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration. In addition, myocardial transcription factors, non-coding RNAs, cyclins, and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation. Ultimately, awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

For boiling water reactors and small reactors, an effective way to reduce containment pressure is to discharge gas from the containment into the suppression pool. Based on the above background, a series of experiments were conducted to investigate the pressure oscillations frequency of steam-air gas discharged into a supercooled water pool. The air mass fraction was 0.0-0.4, and the hole pitch was 1.5d-3d. The air compressor and electric boiler generated air and steam, respectively. The steam and air were mixed and discharged into the supercooled water pool. A high-frequency dynamic pressure sensor was used at the nozzle outlet to record the pressure oscillation signal, and a high-speed camera captures jet plume images. The fast Fourier transform (FFT) was used to process the pressure signal, and the peak value of the frequency domain signal is the dominant frequency of the oscillation. The image observation reveals that in the case of a double-hole jet, the interference of the two gas plumes causes the gas plumes to converge or even agglomerate to form a combined jet. The dominant frequency of the double-hole jet is lower than that of the single-hole jet because of the increase in the dimension of the double-hole jet plume, which leads to a longer condensation time. Therefore, increasing the number of holes will result in a decrease in the dominant frequency of the oscillation, which may be closer to the equipment's natural frequency and lead to resonance damage. For temperature effects, the condensation time of the plume is shorter as the subcooling increases, so the oscillation frequency increases with subcooling. For the effect of hole pitch, the dominant frequency increases with hole pitch. The water temperature between the two gas plumes decreases as the hole pitch increases, and the gas plumes condense faster and take less time to condense. Based on the research conclusions of the dominant frequency characteristics of the steam jet condensation, an empirical equation for predicting the dominant frequency was proposed, and the predicted deviation is within the range of -15%-20%. The oscillation dominant frequency of the steam-air mixture jet increases with the subcooling degree and the hole pitch, which is consistent with the conclusion of the steam jet. When steam-air mixture gas jets, the dominant frequency is inversely proportional to the non-condensable gas mass fraction. The reason is that during the steam-air mixture gas jets, the concentration of non-condensable gas increases after steam condensation between the gas-water interfaces, which inhibits the mass transfer process, resulting in a longer condensation time. As the fraction of non-condensable gases increases, the mass transfer inhibition becomes more pronounced.

BackgroundThe unfolding-synthesis technique is commonly used in digital pulse processing systems for nuclear radiation measurements.PurposeThis study aims to propose a novel flat-topped widened peak-shaping algorithm based on the pulse unfolding-synthesis technique is proposed.MethodsFirstly, the repetition and polynomials were utilizes to shape the digital pulses, and the nuclear pulse signal was unfolded into unit pulses series. Then, an impulse response system was employed to synthesize these unit pulses series to achieve the desired peak shape. Finally, the improved flat-topped peak-shaping algorithm was compared and analyzed against traditional filter shaping algorithms in terms of accuracy in amplitude extraction, interference resistance, and pile-up recognition.ResultsExperimental results demonstrate that, under the same shaping time, the energy resolution of the flat-topped peak-shaping algorithm for the γ characteristic peak of 137Cs is 7.2%, outperforming the trapezoidal, triangular, and Gaussian shaping algorithms. Additionally, it exhibits high counting rate performance.ConclusionsThe flat-topped peak-shaping algorithm of this study can effectively replace traditional pulse-shaping methods and be utilized for high-precision, high-count-rate γ spectroscopy measurements.

Abstract Ketone bodies serve as an energy source, especially in the absence of carbohydrates or in the extended exercise. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a crucial energy sensor that regulates lipid and glucose metabolism. However, whether AMPK regulates ketone metabolism in whole body is unclear even though AMPK regulates ketogenesis in liver. Prolonged resulted in a significant increase in blood and urine levels of ketone bodies in wild-type (WT) mice. Interestingly, fasting AMPKα2–/– and AMPKα1–/– mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. BHB tolerance assays revealed that both AMPKα2–/– and AMPKα1–/– mice exhibited slower ketone consumption compared to WT mice, as indicated by higher blood BHB or urine BHB levels in the AMPKα2–/– and AMPKα1–/– mice even after the peak. Interestingly, fasting AMPKα2–/– and AMPKα1–/– mice exhibited significantly higher levels of ketone bodies in both blood and urine compared to fasting WT mice. . Specifically, AMPKα2ΔMusc mice showed approximately a twofold increase in blood BHB levels, and AMPKα2ΔMyo mice exhibited a 1.5-fold increase compared to their WT littermates after a 48-h fasting. However, blood BHB levels in AMPKα1ΔMusc and AMPKα1ΔMyo mice were as same as in WT mice. Notably, AMPKα2ΔMusc mice demonstrated a slower rate of BHB consumption in the BHB tolerance assay, whereas AMPKα1ΔMusc mice did not show such an effect. Declining rates of body weights and blood glucoses were similar among all the mice. Protein levels of SCOT, the rate-limiting enzyme of ketolysis, decreased in skeletal muscle of AMPKα2–/– mice. Moreover, SCOT protein ubiquitination increased in C2C12 cells either transfected with kinase-dead AMPKα2 or subjected to AMPKα2 inhibition. AMPKα2 physiologically binds and stabilizes SCOT, which is dependent on AMPKα2 activity.

The 1∶500000 seismotectonic map of the Ordos active block and boundary zone is a special achievement of the national key research and development project “Research on dynamic model and strong earthquake risk of Ordos active block boundary zone” . Taking the Ordos active block and boundary zone as the mapping scope, this map refers to the compilation standards and database standards of seismotectonic map in the seismic industry, and carries out high-resolution image interpretation on the basis of systematically collecting and collating geographic information, geology, active tectonics, earthquake, geophysics and other data. It absorbs the latest research results of the project and builds the basic database required for mapping. Through data vectorization, stratigraphic boundary modification, fault modification, map modification, the 1∶500000 seismotectonic map of the Ordos active block and boundary zone was compiled. This map reflects the boundary zone of Ordos active blocks such as Yinchuan Basin Helan Mountains, arc structure bundle, Weihe Basin, Shanxi graben system, Hetao Basin and the seismic structure of adjacent blocks, the geometric and kinematic images of active tectonics in the Ordos block and boundary zone were improved.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

ObjectiveDanhong injection (DHI) is widely used in the treatment of myocardial infarction (MI). We aimed to systematically review the efficacy and safety of DHI in a randomized controlled experiment on MI.MethodsWe searched the randomized controlled trials (RCTs) of DHI for MI published before 2 April 2023 in China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang database, China Science and Technology Journal Database (VIP), PubMed, Web of Science, Cochrance Library, and Embase databases. The methodological quality of the included studies was evaluated using the Cochrane Handbook 5.3 criteria using the RevMan software, and meta-analysis was performed and a forest map was drawn.ResultsA total of 38 trials included 3877 patients, including 2022 cases in the DHI treatment group and 1855 cases in the control group. Meta-analysis showed that the total effective rate (RR = 1.18%, 95% CI [1.14–1.12]) during treatment with DHI was higher than that of the control group. The prevalence of cardiac arrhythmia (RR = 0.55%, 95% CI [0.46–0.65]) was lower than that of the control group. The incidence of heart rate failure (RR = 0.45%, 95% CI [0.30–0.70]) was lower than that of the control group. The prevalence of cardiogenic shock (RR = 0.33%, 95% CI [0.11–1.04]) was p > 0.05, and the difference was not statistically significant. There was no statistically significant difference in LVEF between the two groups (MD = 0.00%, 95% CI [0.00–0.00]). CK-MB (MD = −0.81%, 95% CI [−0.92∼ −0.69]) was lower than the control group. hs-CRP (MD = −1.09, 95% CI [−1.22∼ −0.97]) was lower than the control group. The incidence of adverse reactions (RR = 0.37, The 95% CI [0.17–0.82]) was lower than that in the control group.ConclusionBasing on our study, the use of DHI in the treatment of myocardial infarction patients is effective, can improve cardiac function, reduce the incidence of adverse reactions, and improve the overall quality of life.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023390973.

Summary: The model of M2-like tumor-associated macrophages (TAMs) is an increasingly attractive model for the study of TAMs. However, the detailed process of M2-like TAMs polarization induced by lactic acid or conditioned medium from Lewis cells (LCM) and the identification of M2-like TAMs is not yet available. In this protocol, we present the detailed methods to induce M2-like TAMs polarization and verify its functionality in order to better carry out related research.For complete details on the use and execution of this protocol, please refer to Fang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In this study, six bimetallic rare earth (RE = La, Ce, Pr, Nd, Sm, Eu) cobalt nitrogen doped carbon nanotubes (RECo-NCNTs) were synthesized with g-C3N4 derivative method. These RECo-NCNTs were characterized by SEM, BET, XPS, XRD and Raman. In addition, their catalytic performances for oxygen reduction reaction (ORR) had also been tested. The introduction of rare earths did not destroy the structure of nanotubes but apparently change their ORR performances. The PrCo-NCNTs showed the significant improvement in catalytic ability for ORR (onset potential of 0.95 V and half-wave potential of 0.79 V), which is very close to that of commercial 20 % Pt/C. Moreover, PrCo-NCNTs exhibits an excellent catalytic stability (no activity decay after 10000st cycles) and an outstanding methanol toxic tolerance. Assembled in metal–air batteries (Zn-air, Al-air and Mg-air), the PrCo-NCNTs electrode also presents high power densities and discharge voltages.

Multimodal imaging, which combines the strengths of two or more imaging modalities to provide complementary anatomical and molecular information, has emerged as a robust technology for enhancing diagnostic sensitivity and accuracy, as well as improving treatment monitoring. Moreover, the application of multimodal imaging in guiding precision tumor treatment can prevent under- or over-treatment, thereby maximizing the benefits for tumor patients. In recent years, several intriguing magneto-optical nanosystems with both magnetic and optical properties have been developed, leading to significant breakthroughs in the field of multimodal imaging and image-guided tumor therapy. These advancements pave the way for precise tumor medicine. This review summarizes various types of magneto-optical nanosystems developed recently and describes their applications as probes for multimodal imaging and agents for image-guided therapeutic interventions. Finally, future research and development prospects of magneto-optical nanosystems are discussed along with an outlook on their further applications in the biomedical field.

In order to improve the safety and energy exchange efficiency of electric thermal pyrotechnic devices, a new energy exchange element technology of high energy metal (W) film/aluminum nitride ceramic was explored by taking advantage of the high thermal conductivity of aluminum nitride ceramic materials. High-temperature co-fired ceramics were used to prepare the new system energy exchangers, and the prototype of the new system energy exchanger of high-energy metal (W) film/aluminum nitride was obtained. Through infrared microscopic test and ignition performance test, the new system energy exchanger of high-energy metal (W) film/aluminum nitride can satisfy the 1A1W5min non-ignition test, and the ignition current of 50% is 2.80 A. The response current of 99.9% is 3.54 A, and the response current of 0.1% is 2.06 A, which provides technical support for the application of a new type of passivated electric thermal pyrogenic product.

Pyruvate dehydrogenase complex (PDHC) deficiency is a common genetic disorder leading to lactic acidosis, which can also result from several nongenetic conditions, such as septic shock. The present study reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis. This case involved a 16-year-old adolescent with poor exercise tolerance compared with his peers, and no underlying diseases. The disease onset was characterized by cough, fever, and dyspnea, with hypotension and elevated lactate levels, which indicated septic shock. However, severe hypoglycemia and lactic acidosis persisted despite resolution of a pulmonary infection and correction of septic shock, requiring continuous intravenous infusion of 50% glucose. Although the patient did not experience acute kidney injury and had normal urine output, continuous renal replacement therapy was used to regulate the internal environment owing to the severity of the acidosis. The diagnosis of PDHC deficiency was considered on the basis of the persistent hypoglycemia and hyperlactatemia, before genetic mutation testing was completed. The clinical thinking process required a rich accumulation of pathophysiological knowledge. This article reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.