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Salt freezing damage has severe impacts on durability of cement-based materials (CBMs). Calcined layered double hydroxide (CLDH), as an efficient environmental-friendly adsorption material, can impart excellent salt freezing resistance to CBMs. In this work, salt freezing resistance improvement of CBMs incorporated with CLDH was experimentally evaluated by chloride binding capacity, mass loss rate, relative dynamic elastic modulus, setting time, compressive strength, and micro structure tests. Beside these, the salt freezing damage model was established to effectively express the quantitative relationship between influencing factors and evaluation indexes of the salt freezing resistance of CBMs. Results show that CLDH can reconstruct its original layered structure to form reconstructed layered double hydroxide (RLDH). RLDH combines with chloride ions to form RLDH-Cl recrystallization, which can improve chloride binding capacity and pore structures of CBMs to relieve the salt freezing damage. The salt freezing damage model indicates that the suitable CLDH content can evidently alleviate the salt freezing damage, which facilitates the quantitative analysis of the effect of CLDH on the salt freezing resistance of CBMs.

In recent years, it has been gradually recognized that efficient scheduling of automated guided vehicles (AGVs) can help companies find the balance between energy consumption and workstation satisfaction. Therefore, the energy consumption of AGVs for the manufacturing environment and the AGV energy efficient scheduling problem with customer satisfaction (AGVEESC) in a flexible manufacturing system are investigated. A new multi-objective non-linear programming model is developed to minimize energy consumption while maximizing workstation satisfaction by optimizing the pick-up and delivery processes of the AGV for material handling. Through the introduction of auxiliary variables, the model is linearized. Then, an interactive fuzzy programming approach is developed to obtain a compromise solution by constructing a membership function for two conflicting objectives. The experimental results show that a good level of energy consumption and workstation satisfaction can be achieved through the proposed model and algorithm.

Abstract The nonanalyticity of the Loschmidt echo at critical times in quantum quenched systems is termed as the dynamical quantum phase transition, extending the notion of quantum criticality to a nonequilibrium scenario. In this paper, we establish a new paradigm of dynamical phase transitions driven by a sudden change in the internal spatial correlations of the disorder potential in a low-dimensional disordered system. The quench dynamics between prequenched pure and postquenched random system Hamiltonian reveals an anomalous dynamical quantum phase transition triggered by an infinite disorder correlation in the modulation potential. The physical origin of the anomalous phenomenon is associated with the overlap between the two distinctly different extended states. Furthermore, we explore the quench dynamics between the prequenched random and postquenched pure system Hamiltonian. Interestingly, the quenched system undergoes dynamical quantum phase transitions for the prequench white-noise potential in the thermodynamic limit. In addition, the quench dynamics also shows a clear signature of the delocalization phase transition in the correlated Anderson model.

Diabetes mellitus, an epidemic with a rapidly increasing number of patients, always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization, decreased angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Herein, a poly (lactic-co-glycolic acid) (PLGA)-based microneedle patch loaded with magnesium hydride (MgH2) (MN-MgH2) is manufactured for defeating diabetic wounds. The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH2 that can generate hydrogen (H2) and magnesium ions (Mg2+) after reaction with body fluids. The released H2 reduces the production of ROS, transforming the pathological microenvironment induced by diabetes mellitus. Meanwhile, the released Mg2+ promotes the polarization of pro-healing M2 macrophages. Consequently, cell proliferation and migration are improved, and angiogenesis and tissue regeneration are enhanced. Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H2 and Mg2+ locally and sustainably.

Key Clinical Message Maternally inherited diabetes and deafness (MIDD) is often caused by the m.3243A > G mutation in mitochondrial DNA. Unfortunately, the characteristics of MIDD, especially long‐term outcomes and heteroplasmic changes, have not been well described previously. The purpose of this study was to describe the clinical and genetic features of a family with MIDD after 10 years of follow‐up.A 33‐year‐old male patient with typical characteristics of MIDD, including early‐onset diabetes, deafness, and low body mass index, was admitted to our department. Further investigation revealed that the vast majority of his maternal relatives suffered from diabetes with or without deafness. A detailed family history was then requested from the patient and a pedigree was constructed. The patient suspected of MIDD was screened for mutations using whole mitochondrial DNA sequencing. Candidate pathogenic variants were then validated in other family members through Sanger sequencing. The patient was diagnosed with MIDD, with inherited m.3243A > G mutation in the mitochondrially encoded tRNA leucine 1 (MT‐TL1) gene, after 10 years of symptom onset. The patient was then treated with insulin and coenzyme Q10 to improve mitochondrial function. During the follow‐up period, his fasting blood glucose and HbA1c levels were improved and the incidence of diabetic ketoacidosis was significantly reduced. Our findings indicate that whole mitochondrial DNA sequencing should be considered for patients suspected of MIDD to improve the efficiency of diagnosis and prognosis.

Background It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. Methods and Results In the prospective community‐based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow‐up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency

The prevalence of mathematical difficulties (MD) among primary school children in China and its related factors remain unclear. To provide a suitable foundation for formulating appropriate screening and intervention strategies, this study aimed to estimate the prevalence of MD and its possible factors among primary school children in China. Articles were identified from seven databases and included if they reported on the prevalence of MD among primary school children in China. A total of 30,881 articles were retrieved, 975 of which were subjected to full evaluation. In total, 54 studies involving 34,815 participants (mean age 9.86 ± 3.13 years) were included. Analyses were conducted using the Meta and Metafor packages in the statistical software environment R. We used meta-regression and subgroup analyses by variable type to evaluate the potential prevalence factors. The pooled prevalence of MD among primary school children in China was 8.97%, whereas the prevalence rates of MD in lower, middle, and upper primary schools were 11.57%, 10.07%, and 4.76%, respectively. The results showed that the prevalence of MD among primary school children in China was significantly related to grade level and the cut-off points selected for screening MD and that the prevalence of MD in middle primary school was higher in girls than in boys. The prevalence of MD in primary schools in China was slightly higher than that in countries such as the United Kingdom and the United States. The prevalence of MD was higher in the lower and middle grades of primary school. The grade level and cut-off points selected during MD screening were closely related to the prevalence of MD. More attention should be paid to girls with MD in middle primary school.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023410311, identifier: CRD42023410311.

Observations show that globular clusters (GCs) might be among the best places to find millisecond pulsars (MSPs). However, the GC Terzan 6 seems to be an exception without any pulsar discovered, although its high stellar encounter rate suggests that it harbors dozens of them. We report the discovery of the first radio pulsar, PSR J1750–3116A, likely associated with Terzan 6 in a search of C -band (4–8 GHz) data from the Robert C. Byrd Green Bank Telescope with a spin period of 5.33 ms and dispersion measure (DM) ≃ 383 pc cm ^−3 . The mean flux density of this pulsar is approximately 3 μ Jy. The DM agrees well with predictions from the Galactic free electron density model, assuming a distance of 6.7 kpc for Terzan 6. PSR J1750–3116A is likely an isolated MSP, potentially formed through dynamical interactions, considering the core-collapsed classification and the exceptionally high stellar encounter rate of Terzan 6. This is the highest radio frequency observation that has led to the discovery of a pulsar in a GC to date. While L -band (1–2 GHz) observations of this cluster are unlikely to yield significant returns due to propagation effects, we predict that further pulsar discoveries in Terzan 6 will be made by existing radio telescopes at higher frequencies.

We present the scintillation velocity measurements of FRB 20201124A from the Five-hundred-meter Aperture Spherical radio Telescope observations, which reveal an annual variation. This annual variation is further supported by changes detected in the scintillation arc as observed from the secondary spectrum. We attribute the annual velocity variation to the presence of a moderately anisotropic scattering screen located at a distance of 0.4 ± 0.1 kpc from Earth. Our results prove that the scintillation of this fast radio burst (FRB) is mainly caused by material close to Earth on a Galactic scale. However, scintillation observations of other FRBs may expose their surrounding environment or uncover possible orbital motion if scintillation is caused by materials in their host galaxy.

Introduction EQ-5D is one of the most frequently used health-related quality of life (HRQoL) measures but has been found to be insensitive in detecting differences in health status in some general populations and disease groups. For example, the appropriateness of applying EQ-5D in the Chinese cultural setting has been widely discussed. Adding additional HRQoL dimensions (bolt-on items) can be a solution to both retain the original descriptive system of EQ-5D, while enhancing its sensitivity to the local context. To date, no studies have proposed culturally relevant bolt-ons for China or examined the psychometric properties of such bolt-on items. This protocol documents the identification, development, selection and psychometric testing of culturally relevant bolt-on items for EQ-5D-5L in China.Methods and analysis We will identify and develop candidate bolt-on items that are most relevant in the Chinese culture, through former literature reviews on health concepts important for the Chinese population, conducting expert consultations and qualitative interviews. We will quantitatively test the acceptability and measurement properties (including distributional characteristics and construct validity) of the candidate items in both general and disease populations in a cross-sectional setting. The patient group will be followed up to collect two-time-point data to assess test–retest reliability of the candidate items. Bolt-on item selection will consider both the qualitative and quantitative evidence gathered. This protocol outlines a comprehensive mixed-methods process for identifying, developing, selecting and testing bolt-on items that are relevant and culturally appropriate in China. This study may serve as a guide for similar initiatives in other cultural contexts.Ethics and dissemination This study received ethics approval from the Institutional Review Board of School of Public Health, Fudan University (IRB number: 2022-TYSQ-03-154). Study findings will be disseminated through international peer-reviewed journal articles as well as public, academic presentations at national and international conferences.

Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes simplex virus (HSV) and occasionally cytomegalovirus (CMV). Sintilimab is an immune checkpoint inhibitor (ICI) that can enhance the body’s anti-tumor immune response. However, treatment with ICIs may lead to reactivation of the VZV. Here, we present a case of ARN caused by VZV infection in a patient receiving sintilimab for cervical cancer. A 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer. Based on clinical manifestations, ophthalmological examination, and vitreous humor biopsy, the patient was diagnosed with acute retinal necrosis syndrome secondary to VZV. After receiving systemic antiviral and anti-inflammatory therapy, retinal necrosis lesions and visual function improved. In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction.

Cell-cell interaction (CCI) plays a pivotal role in cellular communication within the tissue microenvironment. The recent development of spatial transcriptomics (ST) technology and associated data analysis methods has empowered researchers to systematically investigate CCI. However, existing methods are tailored to single-cell resolution datasets, whereas the majority of ST platforms lack such resolution. Additionally, the detection of CCI through association screening based on ST data, which has complicated dependence structure, necessitates proper control of false discovery rates due to the multiple hypothesis testing issue in high dimensional spaces. To address these challenges, we introduce RECCIPE, a novel method designed for identifying cell signaling interactions across multiple cell types in spatial transcriptomic data. RECCIPE integrates gene expression data, spatial information and cell type composition in a multivariate regression framework, enabling genome-wide screening for changes in gene expression levels attributed to CCIs. We show that RECCIPE not only achieves high accuracy in simulated datasets but also provides new biological insights from real data obtained from a mouse model of Alzheimer’s disease (AD). Overall, our framework provides a useful tool for studying impact of cell-cell interactions on gene expression in multicellular systems.

ABSTRACT The monkeypox virus, which was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner and isolate patients to prevent outbreaks so that the vulnerable population is protected and the emergence of dangerous monkeypox variants is restrained. In this study, a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox based on a sucrose-aided multiphase aqueous system has been established with an ultra-high sensitivity of a single copy, which is 10 times higher than the existing RPA-CRISPR one-pot method. The entire reaction was completed within 60 min at 37°C. The detection method exhibited good specificity, effectively distinguishing monkeypox from other orthopoxviruses. The detection results could be observed by the naked eye under ultraviolet or blue light, making it highly suitable for home or limited healthcare settings. The assay has solved the incompatibility between the Cas12a cleavage reaction and the RPA reaction and shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox and sets a technical example of using a multiphase aqueous system to establish one-pot RPA-CRISPR detection. IMPORTANCE The monkeypox virus was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) and continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner to prevent outbreaks. This study establishes a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox virus with an ultra-high sensitivity. The assay shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox, which is useful for the prevention of an epidemic.

Such is the hypoxia in solid tumor that Ⅱ-type photodynamic therapy (PDT) has not yet achieved significantly satisfactory consequences. Despite the rapid advancement in nanotechnology-based PDT for alleviating the hypoxic tumor microenvironment, several challenges persist. These include inefficient passive oxygen-supply mechanisms, low stability of oxygen-delivery nanosystems, and the complexity of their modification processes. To address these issues, we developed integrative nanoformulations (HHI NPs) by sequentially inserting biomacromolecule hemoglobin (Hb) and IR783 (photosensitizer) into hollow mesoporous Prussian blue (HPB NPs) through a straightforward and gentle diffusion method. Intriguingly, the resulting hybrid nanocomposites based on hollow mesoporous structure provided stability of biomacromolecule Hb, ensuring active and efficient oxygen delivery. In these nanosystems, HHI NPs equipped with high oxygen-carrying Hb efficiently generated reactive oxygen species over HepG2 cells cultured in hypoxic condition under NIR irradiation. Additionally, HPB NPs served not only as nanocarriers but also as photothermal agents exhibiting excellent photothermal conversion effects. which were beneficial for photothermal therapy (PTT) of cancer. HHI NPs co-loaded with Hb and IR783 not only actively relieved the hypoxic TME through the stable protection of the hollow structure from HPB NPs, but also achieve the significant synergistic therapy by combining PDT and PTT for tumor treatment.

Diabetic tubulopathy (DT) is a recently recognized key pathology of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital pathological factor in different types of metabolic diseases, such as DKD. Finerenone (FIN), a novel non-steroidal mineralocorticoid receptor antagonist, attenuates kidney inflammation and fibrosis in DKD, but the precise pathomechanisms remain unclear. The role of mineralocorticoid receptor (MR) in perturbing mitochondrial function via the PI3K/Akt/eNOS signaling pathway, including mitochondrial dynamics and mitophagy, was investigated under a diabetic state and high glucose (HG) ambiance. To elucidate how the activation of MR provokes mitochondrial dysfunction in DT, human kidney proximal tubular epithelial (HK-2) cells were exposed to HG, and then mitochondrial dynamics, mitophagy, mitochondrial ROS (mitoROS), signaling molecules PI3K, Akt, Akt phosphorylation and eNOS were probed. The above molecules or proteins were also explored in the kidneys of diabetic and FIN-treated mice. FIN treatment reduced oxidative stress, mitochondrial fragmentation, and apoptosis while restoring the mitophagy via PI3K/Akt/eNOS signaling pathway in HK-2 cells exposed to HG ambiance and tubular cells of DM mice. These findings linked MR activation to mitochondrial dysfunction via PI3K/Akt/eNOS signaling pathway in DT and highlight a pivotal but previously undiscovered role of FIN in alleviating renal tubule injury for the treatment of DKD.

Abstract Muscular dystrophy (MD) is a genetic disorder that causes progressive muscle weakness and degeneration. Limb‐girdle muscular dystrophy (LGMD) is a type of MD that mainly causes muscle atrophy within the shoulder and pelvic girdles. LGMD is classified into autosomal dominant (LGMD‐D) and autosomal recessive (LGMD‐R) inheritance patterns. Mutations in the Dysferlin gene (DYSF) are common causes of LGMD‐R. However, genetic screening of DYSF mutations is rare in Taiwan. Herein, we identified a novel c.2867_2871del ACCAG deletion and a previously reported c.937+1G>A mutation in DYSF from a Taiwanese family with LGMD. The primary symptoms of both siblings were difficulty climbing stairs, walking on the toes, and gradually worsening weakness in the proximal muscles and increased creatine kinase level. Through pedigree analysis and sequencing, two siblings from this family were found to have compound heterozygous DYSF mutations (c. 937+1G>A and c. 2867_2871del ACCAG) within the separated alleles. These mutations induced early stop codons; if translated, truncated DYSF proteins will be expressed. Or, the mRNA products of these two mutations will merit the nonsense‐mediated decay, might result in no dysferlin protein expressed. To our knowledge, this is the first report of a novel c.2867_2871del ACCAG deletion in DYSF. Further research is required to examine the effects of the novel DYSF mutation in Taiwanese patients with LGMD.

By integrating calculation of phase diagram (CALPHAD) simulations, ab initio molecular dynamics (AIMD) and experimental validation, we shed light on the unexpected spinodal decomposition in as-cast Al30Co10Cr30Fe15Ni15 alloy, as opposed to the eutectic BCC/B2 microstructure predicted by CALPHAD. We showed that the eutectic high entropy alloy (EHEA) and spinodal decomposition (SD) may be correlated with each other. A shift from as-cast EHEA to SD can be triggered by the strong short-range ordering in the EHEA liquid phase and high configuration entropy of the metastable phase. CALPHAD showed that the low eutectic temperature of Al30Co10Cr30Fe15Ni15 alloy is stabilized by the short-range and topological ordering (SRO), rendering a small undercooling ΔT for partitionless solidification of the metastable B2 phase. AIMD calculations showed that the particular metastable-like liquid preordering might reduce interface energy between the eutectic liquid and saturated B2, facilitating metastable saturated phase formation even with a small undercooling and suppressing the eutectic reaction. The single B2 phase might have solidified in the spinodal region of the phase diagram resulting in a shift from as-cast EHEA to SD. The interplay between SD and EHEAs presents an alternative route to explore spinodal HEAs by simple as-casted samples without lengthy heat treatments for homogenization.

BackgroundOnline medical consultation (OMC) is significant to promote the utilization and accessibility of healthcare resources and save time on consultation. However, the usage and public acceptance rates of it are still low in China. Meanwhile, few studies have focused on consumers’ demand of OMC services. This study aims to identify attributes that influence users’ preference for OMC services, quantify the value of these characteristics, and compare their relative importance.MethodsA nationwide discrete choice experiment was conducted to survey Chinese residents’ preference choices for six attributes of OMC services. Conditional logit model and mixed logit model were used to analyze respondents’ preference. Willingness to pay and heterogeneity were estimated by the mixed logit model.ResultsA total of 856 respondents completed the study, and 668 questionnaires passed the consistency test. All of 6 attributes in the study were statistically significant except for “Doctor’s professional title – Associate Senior.” When choosing OMC services, respondents preferred to spend as little time and money as possible on a large online medical platform to consult a high-rated physician with a senior title from a well-known Grade-A tertiary hospital. Besides, respondents valued doctor’s evaluation score most and were willing to pay ¥107 to obtain the services of higher-scored doctors.ConclusionThe study measured Chinese residents’ preferences for six attributes of OMC and showed the heterogeneity of attributes among subgroups. Our findings suggested that OMC services providers should reduce the customers’ waiting time, improve the quality of services and enhance professional skills to meet the customers’ requirements. More research on preferences for OMC needs to be conducted in China, especially for key populations such as patients with chronic diseases.

Objective To systematically investigate the health-related quality of life (HRQOL) and economic burden of children with pneumonia in different regions of China.Study design The study recruited a series of children under 5 years hospitalised for pneumonia in Shanghai, Zhengzhou and Kunming from January to October 2019.Health utility was assessed using the proxy version of EQ-5D-Y by interviewing patients’ guardians face to face. The assessment was administered twice at patients’ admission and discharge. Cost incurred for receiving the hospitalisation was collected. Multiple linear regression and quantile regression were used to explore factors of EQ-5D-Y Health Utility Score (HUS) and costs, respectively.Results A total of 501 paediatric patients with a median age (IQR) of 1.5 (0.83–2.71) years were included in the analysis. The mean HUS (SD) of the patients was 0.78 (0.18) at admission, and increased to 0.96 (0.10) at discharge. Some patients (14.2%) still felt worried, sad or unhappy after hospitalisation. The mean hospitalisation cost and total cost were RMB5859 (€773) and RMB6439, respectively. The HUS was lower and the economic burden was heavier for the children in Zhengzhou. Apart from region, type of work, insurance status and hospital days were also related to the baseline HUS or HUS increment after treatment; insurance status, Visual Analogue Scale score at discharge, guardians’ employment and hospitalisation days were associated with the costs.Conclusion The children with pneumonia have poor baseline HRQOL, and many of them still have psychological well being problems after treatment. The economic burden varied significantly across regions and is heavy for the patients’ families in less developed areas (ie, Zhengzhou and Kunming).

Objective: Repair of free skin flaps to soft tissue defects is common in the clinic. Arterial crisis is a common complication after free flap surgery. This study aimed to investigate the effect of Fogarty catheter embolectomy combined with catheter-based drug thrombolysis to treat arterial embolism after free flap operation. Methods: Eight patients with soft tissue defects in foot and ankle repair with a free flap were analyzed. All patients received Fogarty catheter embolectomy combining catheter-based drug thrombolysis. Operation time, intraoperative blood loss, arterial patency rate, and complications were recorded. Flap survival was observed, and the curative effect was evaluated by the American orthopedic foot ankle society (AOFAS) score. Results: Among eight patients, six flaps completely survived (primary (I) incision healing), one case had partial flap necrosis (secondary (II) incision healing), and one case developed threatened arterial supply again (secondary (II) healing). The causes of defects included crushing injury (three cases), crush injury (two cases), explosive injury (one case), burn injury (one case), and cutting injury (one case). Excluding one patient who changed to incision and exploration, the artery patency rate in eight patients was 87.5 % (7/8), with an average operation time of 65 min (55–90 min) and an average intraoperative blood loss of 65 ml (35–70 ml). At the last follow-up, the flap survived well, foot and ankle function improved, the satisfactory flap rate was 85.71 % and the excellent/good AOFAS ankle hindfoot function rate was 71.42 %. For the typical patient, after 1.5 years of follow-up, the curative effect of the flap was satisfactory and the AOFAS score was 92, demonstrating excellent ankle function. Conclusions: Fogarty catheter embolectomy combined with catheter-based thrombolysis is minimally invasive, fast, safe, and effective for the treatment of arterial embolism after free flap foot and ankle transplantation.

The Tibet Plateau, with its extensive carbon pools, plays a pivotal role in the global carbon budget. Nevertheless, the driving factors of the carbon dioxide budget remain disputed, and the impact of freeze–thaw process on carbon release is still unclear due to the harsh climate and lack of monitoring data. To clarify the primary factors affecting the alpine meadow ecosystems and to examine the impact of freeze–thaw on carbon release, we employed the LI-8150 automated continuous measurement system. This system, in conjunction with eddy covariance meteorological data, The Boosted Regression Tree (BRT) model, and multiple stepwise regression analysis, were used to analyze the seasonal variations in carbon flux (e.g., net ecosystem carbon exchange [NEE], gross primary productivity [GPP], and ecosystem respiration [Reco]). We also investigate the carbon sources and sinks in the alpine meadow ecosystem, as well as the predominant factor of carbon flux. Our findings include: (1) the carbon sources and sinks in the alpine meadow ecosystem shift seasonally on monthly and daily scales. On a monthly scale, the ecosystem functions as a moderate carbon sink in June, July, August, and September and as a weak carbon source from October through May. (2) Overall, the alpine meadow ecosystem, located in the northeastern Qinghai Lake basin, serves as a weak carbon sink (-58.53 g C m−2 year−1). (3) Soil temperature is the primary factor driving most variations observed in NEE, Reco, and GPP, contributing 48.05 %, 78.61 %, and 65.05 %, respectively. Soil temperature, soil water dynamics influenced by freeze and thaw processes, and their interaction with plant growth collectively play a crucial role in regulating the carbon sources and sinks in ecosystems. We provide first-hand observational data for monitoring the carbon sources and sinks in the alpine meadow ecosystem of the Tibet Plateau, as well as offer future guidance for studying the carbon budget of the Tibet Plateau.

In this work, a new design principle, i.e. doping with refractory metal particles with a low diffusion rate to prevent the formation of cracks and to improve the mechanical properties of bulk metallic glass (BMG) composites, was put forward. It was proven that crack-free and dense Mo(p)/Cu47Zr47Al6 BMG composites with enhanced mechanical properties can be produced via LPBF. The dislocations generated in the Mo particles can release thermal stress, thereby inhibiting the formation of thermal-cracks. The fracture patterns of Mo particles show that they can delay rapid of crack expansion, thereby improving the inherent strength and toughness of the material.

In this study, we assessed the effects of MFG-E8 on the biological characteristics of ovarian cancer cells and explored the underlying mechanisms. Human ovarian cancer SKOV3 cells were transfected with MFG-E8 siRNA or NC siRNA. CCK-8, cell adhesion, scratch-wound, and Transwell assays were used to detect changes in cell metastatic processes. Effects of MFG-E8 silencing on the proteins involved in AKT/mTOR/S6K signalling pathway were assessed using qRT-PCR and Western blotting. Transient silencing of MFG-E8 in SKOV3 cells decreased cell proliferation and downregulated the expression of CDK4, cyclin D1, and caspase-3 proteins. Cell adhesion, migration, and invasion were also suppressed. p-AKT, p-mTORC1, and p-p70S6K levels decreased following MFG-E8 knockdown. Hence, MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signalling pathway in ovarian cancer cells. In conclusion, our results suggested that MFG-E8 could promote ovarian cancer via AKT/mTOR/S6K signalling pathway which improved our understanding of the molecular mechanisms involved in ovarian cancer.IMPACT STATEMENT What is already known on this subject? Milk fat globule-epidermal growth factor 8 (MFG-E8) is expressed in several types of cancers such as oesophageal, breast, and liver. However, the mechanism of MFG-E8 involving in EOC remains unknown. We previously found that MFG-E8 expression was related to pathological staging, tissue differentiation, platinum sensitivity, ascites state, and other clinicopathological characteristics. What the results of this study add? Due to a series of in vitro studies, we confirmed that MFG-E8 is involved in the process of proliferation, invasion and metastasis. Our results show that silencing MFG-E8 can significantly inhibit the expression of cyclin D1 and CDK4 in EOC SKOV3 cells. MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signaling pathway in ovarian cancer. What the implications are of these findings for clinical practice and/or further research? Taken together, our findings suggest that MFG-E8 may be an oncogene in EOC and provide new insights into the mechanism of MFG-E8 in the progression of EOC.

Abstract Background Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. Methods Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. Results Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1β, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1β, IL-18, HMGB1 and the cleaved form of GSDMD. Conclusions Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

[Objective] The granularity characteristics of surface sediments in the Arexunula Desert in Xinjiang Uygur Autonomous Region were studied in order to understand the characteristics of surface sediments in the study area and the factors affecting the granularity distribution of sediments. [Methods] Granularity was divided into grains, granularity parameters, and fractal dimension of the surface sediments for the Arexunula Desert and sand dunes in Xinjiang were analyzed. [Results] ① The granularity size of surface sediments in the study area was 284.63 μm, with medium sand dominant, accounting for 48.93%. The skewness was -0.18, with a negative bias, close to the sand source. The transport medium had strong dynamics. The sorting coefficient was 1.10, and the sorting performance was excellent. The kurtosis value was 1.01, which was a normal peak state, and the sediment particles were evenly distributed. ② The skewness values of surface sediments of mobile sand dunes and semi-fixed sand dunes were -0.13 and -0.08, respectively, which indicated negative skewness and medium skewness, respectively, and there was a large amount of coarse gravel in both types of dunes. The sorting coefficients were 1.66 and 1.76, both of which were medium, and the sediment granularity distribution was relatively uniform. The kurtosis values were 1.10 and 1.12, respectively, which were normal and narrow peaks, indicating that the coarse-grained sediments of sand dunes were relatively concentrated in the desert. ③ The average granularity values of surface sediments from the bottom of the windward slope to the bottom of the leeward slope were 289.58, 310.44, 290.92, 277.64, 275.36, 310.34 and 306.68, 337.78, 290.36, 277.68 μm, respectively. The coarse-particle sediments of the two types of sand dunes were concentrated in the windward slope. The coarse particle sediment content of the semi-fixed dune windward slope was higher than that of the mobile dune windward slope, and the semi-fixed sand dune had stronger sand interception ability. The sorting coefficients of mobile sand dunes and semi-fixed sand dunes changed from the bottom of the windward slope to the bottom of the leeward slope. The former fluctuated greatly and showed a W-shape, and the latter changed little and was V-shaped. Shrub vegetation made the sorting coefficient change trend turn at the top of the dune. ④ The fractal dimension value of the grain size of desert surface sediments was 1.35, and the fractal dimension values of the particle size of semi-fixed sand dunes and mobile sand dunes were 1.59 and 1.34, respectively. The fluctuation intensity of fractal dimension affected the uniformity of sediment particle distribution, soil fertility, and vegetation growth. [Conclusion] The Arexunula Desert is close to the sand source, and the coarse-grained sediments of the dunes were relatively concentrated in the desert. Shrubland is one of the factors affecting the granularity distribution characteristics of surface sediments.

A decentralized supply chain network under uncertain cost is studied to obtain the optimal decisions of the enterprises in a situation in which the cost is uncertain. The supply chain network members adopt a chance-constrained approach to make decisions. The second-order cone-constrained variational inequality problem is used to construct the chance-constrained supply chain network equilibrium model. Then, the existence and uniqueness properties of the proposed equilibrium model are discussed under some mild assumptions. For the discontinuous functions in the feasible region of the model, the proposed model is converted to a second-order cone complementarity problem. The numerical results show that the uncertainty and risk attitude of retailers and manufacturers have different effects on supply chain network members. When the risk attitude is high, a small change in the risk attitude will significantly change all decisions of supply chain members. If the supply chain member is affected by the uncertainty positively, its profit will increase as its risk attitude increases. Moreover, it is appropriate to adopt a chance-constrained approach when the supply chain members can estimate the distributions of the competitor's strategies.

Developing novel, safe, and efficient proangiogenic drugs is an important approach for the prevention and treatment of cardiovascular diseases. In this study, 4 new compounds, including 3 azaphilones (1–3) and 1 dihydroisocoumarin (4), as well as 13 known compounds (5–17), were isolated from the sea-mud-derived fungus Neopestalotiopsis sp. HN-1-6 from the Beibu Gulf of China. The structures of the new compounds were determined by NMR, MS, ECD, and NMR calculations. Compounds 3, 5, and 7 exhibited noteworthy proangiogenic activities in a zebrafish model at a concentration of 40 μM, without displaying cytotoxicity toward five human cell lines. In addition, some compounds demonstrated antibacterial effects against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64 μg/mL to 256 μg/mL.

Intergenerational justice entitles the maximum retention of Earth’s biodiversity. The 2022 United Nations COP 15, “Ecological Civilisation: Building a Shared Future for All Life on Earth”, is committed to protecting 30% of Earth’s terrestrial environments and, through COP 28, to mitigate the effects of the climate catastrophe on the biosphere. We focused this review on three core themes: the need and potential of reproduction biotechnologies, biobanks, and conservation breeding programs (RBCs) to satisfy sustainability goals; the technical state and current application of RBCs; and how to achieve the future potentials of RBCs in a rapidly evolving environmental and cultural landscape. RBCs include the hormonal stimulation of reproduction, the collection and storage of sperm and oocytes, and artificial fertilisation. Emerging technologies promise the perpetuation of species solely from biobanked biomaterials stored for perpetuity. Despite significant global declines and extinctions of amphibians, and predictions of a disastrous future for most biodiversity, practical support for amphibian RBCs remains limited mainly to a few limited projects in wealthy Western countries. We discuss the potential of amphibian RBCs to perpetuate amphibian diversity and prevent extinctions within multipolar geopolitical, cultural, and economic frameworks. We argue that a democratic, globally inclusive organisation is needed to focus RBCs on regions with the highest amphibian diversity. Prioritisation should include regional and international collaborations, community engagement, and support for RBC facilities ranging from zoos and other institutions to those of private carers. We tabulate a standard terminology for field programs associated with RBCs for publication and media consistency.

The unmanned farm control platform is of great significance in promoting the supervision of farm production with less manpower or autonomous operation of farm machinery and the construction of farm informatization. Addressing the existing control platform for farm location information acquisition is time-consuming, labor-intensive, and lacks the whole process control of multiple types of farm machinery. In this paper, we propose an Internet of Things (IoT) control scheme for intelligent farm machinery operation of unmanned farms and design the access standards for multiple types of farm machinery, as well as realize the remote control of intelligent farm machinery operation by constructing a remote control model. A high-precision map construction method is designed to improve the DeepLabV3+ algorithm to identify fields and roads. The control models of path planning, remote task, remote control, and safety system are built to achieve the remote control of intelligent agricultural machinery operation. The proposed technology is implemented in the platform integration and application tests are carried out. The error of the constructed high-precision map is less than 3 cm, the completeness rate of the automatic boundary extraction rate is 96.71%, and the correctness rate is 95.63%, which can be used to obtain the boundary instead of manual labeling or on-site point picking. The use of the platform for the simultaneous control of three farm machinery operations reduces the number of people in operation and production and reduces the professional requirements of the personnel, which will promote the management of the entire farm by one person or even by no one in the future.

To address public participation-oriented, large group decision-making problems with uncertain attribute weights, we propose a multi-attribute decision-making method considering public satisfaction. Firstly, a large group is organized to provide their opinions in the form of linguistic variables. Public opinions can be categorized into two types based on their content: one reflects the effectiveness of an alternative implementation and the other reflects the public expectations. Secondly, the two types of public opinions are sorted separately by linguistic variables. The evaluation of alternatives and the evaluation of expectations in different attributes are determined, both of which are expressed in the form of linguistic distributions. These two evaluations are then compared to determine the public satisfaction of the attributes in different alternatives. Thirdly, based on the deviation of public satisfaction in different attributes, a weight optimization model is constructed to determine the attribute weights. Fourthly, leveraging the interval credibility of attribute satisfaction for various alternatives, an evidential reasoning non-linear optimization model is established to obtain the comprehensive utility evaluation value for each alternative, which is used for ranking. Finally, a numerical example is employed to validate the feasibility and effectiveness of the proposed approach. According to the results of the numerical example, it can be concluded that the proposed approach can be effectively applied to large group decision-making problems that consider public satisfaction. Based on the comparison of methods, the proposed approach has certain advantages in reflecting public opinions and setting reference points, which can ensure the reliability of the decision results.

The consumption of edible vegetable oil is an important source of essential fatty acids and vitamin E for the human body. Guiding residents to consume scientifically and reasonably control the intake of edible oils is an important part of promoting the construction of a healthy China. Currently, Chinese residents have an insufficient understanding of the scientific consumption of edible oils, leading to an intake exceeding the dietary recommendations, resulting in excessive fat intake and increasing the risk of chronic diseases such as obesity and cardiovascular diseases. Based on the Theory of Planned Behavior (TPB) and using Structural Equation Modeling (SEM), this study analyzed the cognitive preferences and willingness to pay a premium for edible vegetable oils among urban consumers in China. The survey included 1098 Chinese urban consumers of vegetable oils. The research found that attitudes, health value, monetary value, and environmental endowment of urban residents are the main predicting factors of the intention to purchase high-quality vegetable oils. This study confirms the applicability of the Theory of Planned Behavior in the consumption of high-quality vegetable oils and provides theoretical contributions and insights for Chinese enterprises and policymakers in formulating marketing strategies for vegetable oils.

This study utilized bismaleimide (BMI) resin, reinforced with introduced ether bonds, as a binding matrix, in combination with silicon carbide (SiC), for the fabrication of composite materials. A thorough investigation was conducted to assess the influence of diverse processing parameters on the mechanical properties and high-temperature thermo-oxidative stability of these composites. Experimental results indicate a notable improvement in the mechanical properties of the composites upon the incorporation of ether bonds, in contrast to their unmodified counterparts. The variation in performance among composites with different ratios and molding densities is apparent. Within a certain range, an increase in resin content and molding density is correlated with improved bending strength in the composites. With a resin content of 27.5 vol% and a molding density of 2.31 g/cm3, the composite achieved a maximum flexural strength of 109.52 MPa, representing a 24% increase compared to its pre-modification state. Even after exposure to high-temperature heat treatment, the composites displayed commendable mechanical properties compared to their pre-ether bond modification counterparts, maintaining 74.5% of the strength of the untreated composites at 300 °C. The scanning electron microscopy (SEM) microstructures of composite materials correlate remarkably well with their mechanical properties.

Currently, the sol-gel technique is employed in the synthesis of high-performance vitrified bonds; however, its application in the fabrication of stacked abrasives has been minimally explored. Furthermore, the methods utilized in the production of abrasive particles for stacked abrasives are technically challenging and incur high costs, which hinders their actual industrial application. Consequently, this study utilizes the sol-gel approach to synthesize a Na2O-B2O3-SiO2 ternary system vitrified bond powder and employs a molding and crushing method, which offers a lower technological barrier and reduced preparation costs, for the production of abrasive particles subsequently fabricating corundum stacked abrasives. Upon setting the binder composition to a molar ratio of n(SiO2):n(B2O3):n(Na2O) = 65:23:12, it was observed that the crystallization within the glass matrix was minimized and the optimal sintering temperature for the synthesized laminate abrasive to be sustained at 820 °C. At the aforementioned temperature, the binder melt is capable of flowing uniformly amongst the abrasive granules, thereby ensuring a robust encapsulation of the particles. The average single particle compressive strength of the prepared corundum stacked abrasive with a grain size of forty mesh can reach the highest of all composition points at 28.56 N and the average single particle compressive strength of the prepared diamond stacked abrasive is 28.14 N.

Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are versatile drug nanocarriers with a wide spectrum of applications owing to their extensive advantages, including biodegradability, non-toxic side effects, and low immunogenicity. Among the numerous nanoparticle preparation methods available for PLGA NPs (the hydrophobic polymer), one of the most extensively utilized preparations is the sonicated-emulsified solvent evaporation method, owing to its simplicity, speed, convenience, and cost-effectiveness. Nevertheless, several factors can influence the outcomes, such as the types of concentration of the surfactants and organic solvents, as well as the volume of the aqueous phase. The objective of this article is to explore the influence of these factors on the properties of PLGA NPs and their drug release behavior following encapsulation. Herein, PLGA NPs were fabricated using bovine serum albumin (BSA) as a surfactant to investigate the impact of influencing factors, including different water-soluble organic solvents such as propylene carbonate (PC), ethyl acetate (PA), and dichloromethane (DCM). Notably, the size of PLGA NPs was smaller in the EA group compared to that in the DCM group. Moreover, PLGA NPs showed excellent stability, ascribed to the presence of the BSA surfactant. Furthermore, PLGA NPs were co-loaded with varying concentrations of hydrophilic drugs (doxorubicin hydrochloride) and hydrophobic drugs (celecoxib), and exhibited pH-sensitive drug release behavior in PBS with pH 7.4 and pH 5.5.

PurposeThe relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs.MethodsIn this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann–Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility.ResultsPCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p

AimTo explore the effects of brain–computer interface training combined with mindfulness therapy on Hemiplegic Patients with Stroke.BackgroundThe prevention and treatment of stroke still faces great challenges. Maximizing the improvement of patients’ ability to perform activities of daily living, limb motor function, and reducing anxiety, depression, and other social and psychological problems to improve patients’ overall quality of life is the focus and difficulty of clinical rehabilitation work.MethodsPatients were recruited from December 2021 to November 2022, and assigned to either the intervention or control group following a simple randomization procedure (computer-generated random numbers). Both groups received conventional rehabilitation treatment, while patients in the intervention group additionally received brain–computer interface training and mindfulness therapy. The continuous treatment duration was 5 days per week for 8 weeks. Limb motor function, activities of daily living, mindfulness attention awareness level, sleep quality, and quality of life of the patients were measured (in T0, T1, and T2). Generalized estimated equation (GEE) were used to evaluate the effects. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300070382).ResultsA total of 128 participants were randomized and 64 each were assigned to the intervention and control groups (of these, eight patients were lost to follow-up). At 6 months, compared with the control group, intervention group showed statistically significant improvements in limb motor function, mindful attention awareness, activities of daily living, sleep quality, and quality of life.ConclusionBrain–computer interface combined with mindfulness therapy training can improve limb motor function, activities of daily living, mindful attention awareness, sleep quality, and quality of life in hemiplegic patients with stroke.ImpactThis study provides valuable insights into post-stroke care. It may help improve the effect of rehabilitation nursing to improve the comprehensive ability and quality of life of patients after stroke.Clinical review registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300070382.

AimsThe primary aim was to explore the age dependency of health state values derived via trade-offs between health-related quality of life (HRQoL) and life years in a discrete choice experiment (DCE). The secondary aim was to explore if people weigh life years and HRQoL differently for children, adolescents, adults, and older adults.MethodsParticipants from the general population of the Netherlands and China first completed a series of choice tasks offering choices between two EQ-5D-Y states with a given lifespan. The choice model captured the value of a year in full health, disutility determined by EQ-5D-Y, and a discount rate. Next, they received a slightly different choice task, offering choices between two lives that differed in HRQoL and life expectancy but produced the same number of quality-adjusted life years (QALYs). Participants were randomly assigned to fill out the survey for three or four age frames: a hypothetical person of 10, 15, 40, and 70 years (the last one only applicable to China) to allow the age dependency of the responses to be explored.ResultsA total of 1,234 Dutch and 1,818 Chinese people administered the survey. Controlling for time preferences, we found that the agreement of health state values for different age frames was generally stronger in the Netherlands than in China. We found no clear pattern of differences in the QALY composition in both samples. The probability distribution over response options varied most when levels for lifespan or severity were at the extremes of the spectrum.Conclusion/discussionThe magnitude and direction of age effects on values seemed dimension- and country specific. In the Netherlands, we found a few differences in dimension-specific weights elicited for 10- and 15-year-olds compared to 40-year-olds, but the overall age dependency of values was limited. A stronger age dependency of values was observed in China, where values for 70-year-olds differed strongly from the values for other ages. The appropriateness of using existing values beyond the age range for which they were measured needs to be evaluated in the local context.

Since their high power-to-volume property, electric machines with 3D magnetic flux (3D-flux) structure are of great current interest. In them, the flux path is typically achieved by utilizing a soft magnetic composite (SMC) material to minimize the eddy current losses. Here, laser powder bed fusion (LPBF) technique is employed to manufacture a soft magnetic core (Fe-3.5 wt%Si alloy) with the following advantages: i) the (001) texture of Fe-Si alloy is well aligned with the Z direction of the 3D-flux path, which is the easiest magnetization direction in the cubic system; ii) the strength and ductility of the annealed alloy are far superior to those of SMCs. The alternating-current ring method was employed to measure the magnetic properties and a simulation of the 3D-flux electric machine was conducted. The results illustrated that the rotary torque generated with the additively manufactured alloy is 19.1% higher than that of SMCs in the weak magnetic field excited by ferrite at the 50 Hz frequency. However, it is important to note that the additively manufactured alloy also exhibited higher total iron loss in strong magnetic field and high electric frequency, indicating a need for further research to optimize the microstructure and reduce losses for medium/high frequency applications.

Background: Patients undergoing maintenance hemodialysis (MHD) experience insomnia frequently. Poor sleep quality impairs the quality of life and adversely affects long-term outcomes. Currently, the treatment of insomnia in patients undergoing MHD is mainly based on medication, although it has severe side effects and poor compliance in patients. Therefore, developing complementary and alternative therapies with higher efficacies is important. This study explores the clinical efficacy and safety of Tongdutiaoshen acupuncture in treating insomnia in patients with MHD. Methods: This randomized controlled trial (RCT) will be performed at Beijing Luhe Hospital, affiliated with Capital Medical University in China. We will strictly adhere to the Standards for Reporting Interventions in Clinical Trials of Acupuncture (2010). A total of 110 MHD patients with insomnia will be randomly allocated in a 1:1 ratio to the drug control (DC) or Tongdutiaoshen acupuncture (TA) group. Patients in the control group will be administered estazolam tablets (1 mg/day) for four weeks, followed by a 4-week follow-up period. Based on the background therapy provided for the DC group, the TA group will be administered the interventional cohort three times a week for four weeks in a row, followed by a 4-week follow-up period. The primary endpoints will include the Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAM-A), TCM Insomnia Syndrome Score, and clinical response rate, which will be evaluated on days 0, 14, 28, and 56. Secondary endpoints will include sleep data monitoring and related laboratory indices, which will be evaluated on days 0, 28, and 56, respectively. Discussion: This study is designed based on a rigorous methodology to evaluate the efficacy and safety of Tongdutiaoshen acupuncture for insomnia in patients undergoing hemodialysis. The findings of this trial will be published in peer-reviewed journals as reliable evidence. Trial registration: Chinese Clinical Trial Registry ChiCTR2200061967. Registered on July 07, 2022.

Hyperbaric oxygen therapy is a relatively safe treatment method that has been used for a long time in the clinic. It has been proven that it can enhance the sensitivity of radiotherapy and photodynamic therapy for cancer. However, there are few studies on hyperbaric oxygen and immunotherapy. In this article, we summarize that hyperbaric oxygen therapy regulates the tumor microenvironment through various pathways such as improving tumor hypoxia, targeting hypoxia-inducing factors, and generating reactive oxygen species. The change in the tumor microenvironment ultimately affects the curative effect of immunotherapy. Therefore, hyperbaric oxygen can influence immunotherapy by regulating the tumor microenvironment, providing a direction for the future development of immunotherapy.

Background : De qi , the needling sensation, is important in acupuncture treatment. Almost all studies believe that deep needling and manipulation could achieve a significant de qi sensation. However, relatively few studies have examined the effect of psychological factors on de qi, and those that did often reached different conclusions. Objectives: To explore the influence of psychologic factors on de qi in patients with primary dysmenorrhea (PD). Methods : Sixty-eight PD patients with cold and dampness stagnation were randomly allocated to de qi (deep insertion using thick needles, with manipulation, n=17) and non-de qi groups (shallow insertion using thin needles, without manipulation, n=51). Both groups received bilateral needling at Sanyinjiao (SP6) for 30 min. De qi was assessed using the Acupuncture De qi Clinical Assessment Scale (ADCAS). The patients’ acupuncture-related anxiety and their expectations of the relationship between needle sensation and curative effect were evaluated using a five-point and four-point scale, respectively. Results : Within the de qi group, all patients experienced the de qi sensation, although anxiety levels were unrelated to de qi. Patients’ expectations correlated negatively with de qi timing, and positively with electric sensation. Within the non-de qi group, 59.5% of patients experienced de qi. Between those who experienced it and those who did not, no significant differences were found in anxiety levels, although patients’ expectations differed significantly. Among patients who experienced de qi sensations in the non-de qi group, anxiety and throbbing were positively correlated. Additionally, patients’ expectations correlated positively with de qi intensity, as well as coldness, and numbness. Conclusion : Psychological factors should be considered when studying de qi since PD patients’ expectations could influence the de qi sensation at SP6.

Abstract Vibrio species (Vibrio sp.) is a class of Gram-negative aquatic bacteria that causes vibriosis in aquaculture, which have resulted in big economic losses. Utilization of antibiotics against vibriosis has brought concerns on antibiotic resistance, and it is essential to explore potential antibiotic alternatives. In this study, seven compounds (compounds 1–7) were isolated from the Arctic endophytic fungus Penicillium sp. Z2230, among which compounds 3, 4, and 5 showed anti-Vibrio activity. The structures of the seven compounds were comprehensively elucidated, and the antibacterial mechanism of compounds 3, 4, and 5 was explored by molecular docking. The results suggested that the anti-Vibrio activity could come from inhibition of the bacterial peptide deformylase (PDF). This study discovered three Penicillium-derived compounds to be potential lead molecules for developing novel anti-Vibrio agents, and identified PDF as a promising antibacterial target. It also expanded the bioactive diversity of polar endophytic fungi by showing an example in which the secondary metabolites of a polar microbe were a good source of natural medicine. Graphical Abstract

Abstract Type I interferons (IFN-Is) have been harnessed for cancer therapies due to their immunostimulatory functions. However, certain tumor-tolerating activities by IFN-Is also exist, and may potentially thwart their therapeutic effects. In this respect, our previous studies have demonstrated a monocyte-orchestrated, IFN-I-to-IL-4 cytokine axis, which can subsequently drive M2-skewed pro-tumoral polarization of macrophages. Whether other IFN-dependent signals may also contribute to such an unconventional circumstance of M2-like macrophage skewing remain unexplored. Herein, we first unveil IL-6 as another ligand that participates in IFN-dependent induction of a typical M2 marker (ARG1) in transitional monocytes. Indeed, IL-6 significantly promotes IL-4-dependent induction of a major group of prominent M2 markers in mouse bone marrow-derived macrophages (BMDMs) and human peripheral blood-derived macrophages, while it alone does not engage marked increases of these markers. Such a pattern of regulation is confirmed globally by RNAseq analyses in BMDMs, which in turn suggests an association of IL-6-amplified subset of M2 genes with the ERK1/2 signaling pathway. Interestingly, pharmacological experiments establish the role of SHP2-ERK cascade in mediating IL-6’s enhancement effect on these M2 targets. Similar approaches also validate the involvement of IL-6/ERK signaling in promoting the IFN-dependent, unconventional M2-skewing phenotype in transitional monocytes. Furthermore, an inhibitor of ERK signaling cooperates with an IFN-I inducer to enable a greater antitumor effect, which correlates with suppression of treatment-elicited ARG1. The present work establishes a role of IL-6/ERK signaling in promoting M2-like macrophage polarization, and suggests this axis as a potential therapeutic target for combination with IFN-I-based cancer treatments.

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

Conventional transcriptome-wide association study (TWAS) approaches predict genetically regulated gene expression at the tissue level. Here, the authors develop a framework for cell-type-aware TWAS that predicts cell-type level expression from genotype data and identifies disease-associated genes with cell-type-specific effects.

Abstract Background The purpose of this work was to obtain the dosimetric parameters of the new GZP3 60Co high-dose-rate afterloading system launched by the Nuclear Power Institute of China, which is comprised of two different 60Co sources. Methods The Monte Carlo software Geant4 and EGSnrc were employed to derive accurate calculations of the dosimetric parameters of the new GZP3 60Co brachytherapy source in the range of 0–10 cm, following the formalism proposed by American Association of Physicists in Medicine reports TG43 and TG43U1. Results of the two Monte Carlo codes were compared to verify the accuracy of the data. The source was located in the center of a 30-cm-radius theoretical sphere water phantom. Results For channels 1 and 2 of the new GZP3 60Co afterloading system, the results of the dose-rate constant (Λ) were 1.115 cGy h−1 U−1 and 1.112 cGy h−1 U−1, and for channel 3 they were 1.116 cGy h−1 U−1 and 1.113 cGy h−1 U−1 according to the Geant4 and EGSnrc, respectively. The radial dose function in the range of 0.25–10.0 cm in a longitudinal direction was calculated, and the fitting formulas for the function were obtained. The polynomial function for the radial dose function and the anisotropy function (1D and 2D) with a $$\uptheta$$ θ of 0°–175° and an r of 0.5–10.0 cm were obtained. The curves of the radial function and the anisotropy function fitted well compared with the two Monte Carlo software. Conclusion These dosimetric data sets can be used as input data for TPS calculations and quality control for the new GZP3 60Co afterloading system.

No current RNA-targeted interference tools have been reported to simultaneously up and down-regulate different gene expressions. Here we characterized an RNA-targeted genetic regulatory strategy composed of a flap endonuclease 1 (FEN1) and specific mis-hairpin DNA probes (mis-hpDNA), to realize the orthogonal genetic regulation. By targeting mRNA, the strategy hindered the translation and silenced genes in human cells with efficiencies of ~60%. By targeting miRNA, the strategy prevented the combination of miRNA to its specific mRNA and increased this mRNA expression by about 3-folds. In combination, we simultaneously performed CXCR4 gene knock-down (~50%) and EGFR gene activation (1.5-folds) in human cells. Although the functional property can be further improved, this RNA-targeted orthogonal genetic regulating strategy is complementary to classical tools.