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Abstract Objective To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent radiotherapy combined with weekly chemotherapy in patients with cervical cancer. Methods From September 2019 to November 2020, 180 patients with cervical cancer who required concurrent chemoradiotherapy (CCRT) were enrolled in this study. The patients were randomly divided into the following three groups at a ratio of 1:1:1: Group A (PEG-rhG-CSF), Group B (PEG-rhG-CSF + rhG-CSF) and the control group (rhG-CSF). Cisplatin or carboplatin was administered weekly. The primary endpoint was the incidence of grade 3/4 neutropenia. The secondary endpoints were the incidence of febrile neutropenia (FN), delay of radiotherapy, chemotherapy dose reduction, rate of PFS at 2 years and 3 years, and incidence of adverse reactions. Results Sixty patients were randomly assigned to each group. Two patients in Group B withdrew from the trial for personal reasons. The incidence of grade 1/2 neutropenia in the Control group was significantly lower than that in Group A and Group B (P

Abstract Background Craniopharyngioma is a rare and slow-growing benign sellar or parasellar epithelial tumor. The number of patients receiving proton beam therapy (PBT) has increased. This study aimed to systematically evaluate and analyze the comprehensive evidence regarding the safety and efficacy of PBT for craniopharyngioma. Methods We searched four databases: the Cochrane Library, PubMed, Embase, and Web of Science. The period was from their inception to February 16, 2024. Two researchers independently screened the literature and extracted data. Results Among 486 candidate articles, eight studies were included in our study. Exactly 393 patients with craniopharyngioma underwent PBT in these studies. These studies reported data on survival and toxicity. The median sample size was 42.5 patients. The median age was 9.1–37 years; the female proportion was 48.9%, and the median follow-up time was 29–91.4 months. All patients were treated once daily, five times a week, with a fraction of 1.8 Gy (RBE) per session. The median total dose was 54.0 Gy (RBE). The local control rates at 3 and 5 years in these studies were 99% and 93%, respectively. The overall survival rates at 3 and 5 years in these studies were both 100%. The incidence of acute and late toxicities was mainly grade 1–2. The main late toxicities included vascular and visual toxicities, hypothalamic obesity, endocrinopathy, and panhypopituitarism. Conclusions PBT for craniopharyngioma, especially in children and adolescents, has shown impressive local control and acceptable acute and late toxicities.

Abstract In 2018, African swine fever virus (ASFV) emerged in China, causing extremely serious economic losses to the domestic pig industry. Infection with ASFV can cause disseminated coagulation, leading to the consumption of platelets and coagulation factors and severe bleeding. However, the mechanism of virus-induced coagulation has yet to be established. In our study, ASFV downregulated the coagulation process, as detected by D-dimer (D2D) and Factor X (F10) expression in pigs challenged with ASFV HLJ/18. In vitro, ASFV infection increased Factor IX (F9) and Factor XII (F12) expression while downregulating F10 expression in porcine alveolar macrophages (PAMs). African swine fever virus induced both intrinsic and extrinsic coagulation cascades. In addition, several encoded proteins affect the expression of the crucial coagulation protein F10, and among the encoded proteins, p72 inhibits the activity and expression of F10. Proteomic analysis also revealed that p72 is involved in the coagulation cascade. p72 can interact with F10, and its inhibitory functional domains include amino acids 423–432 and amino acids 443–452. Finally, we found that F10 and p72 interact with tripartite motif-containing protein 28 (TRIM28). TRIM28 knockdown resulted in a decrease in F10 expression. Importantly, TRIM28 contributes to the reduction in F10 protein expression regulated by p72. Our findings revealed an inhibitory effect of the viral protein p72 on the ASFV infection-induced coagulation cascade and revealed a role of TRIM28 in reducing F10 expression, revealing a molecular mechanism of ASFV-associated coagulation.

Abstract Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.

Preservation conditions are key to enriching shallow shale gas. Therefore, the veins of two typical wells in the Shixi syncline in northern Guizhou as research objects. Based on core observation, vein thin-section observation, cathodoluminescence, calcite in situ U-Pb dating, fluid inclusion microthermometry, Raman spectrum shift, single well basin simulation, and C-O isotope geochemical analysis, the researchers clarified the characteristics of the veins and the differences in paleofluid activity, as well as their significance for shale gas preservation. The results showed that: 1) a small number of high-angle fractures had developed mainly in the Shixi syncline in northern Guizhou. The width of viens is small and filled primarily with early calcite-quartz and late calcite. The inclusions were mainly methane and brine. The proportion of brine inclusions in the SD1 well was greater than that in the SX1 well. The SD1 well has experienced more intense second-stage uplift and denudation, and the consequent gas loss is serious. 2) The results of the C-O isotope analysis showed that most of the vein-forming fluids were derived from marine carbonate rocks. The O3b had obvious negative deviations of δ13C and δ18O, which were modified by exogenous or deep hydrothermal fluid. The C-O isotope difference between the vein bodies and the surrounding rock of the SX1 well was small, and the preservation conditions were better. 3) The difference in gas content in the Shixi syncline depends on the degree of damage to gas reservoir preservation conditions caused by burial depth and other factors. Shixi syncline is a wide and gentle syncline with central retention enrichment mode. Therefore, clarifying the development of shale veins, the characteristics of paleofluid activity, and their significance for shale gas preservation can lay a foundation for studying the enrichment mechanism of shallow shale gas and thus guide further exploration and development.

Abstract Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models. The results show that impaired mitophagy exists in RGCs of our experimental glaucomatous model. In vivo, PR-619 increased RGCs survival in glaucomatous rats. In vitro, it protected RGCs against excitotoxicity and reduced ubiquitin-specific protease (USP) 15 expression. Additionally, PR-619 upregulated parkin expression, increased LC3-II/LC3-I ratios, and elevated LAMP1 levels, indicating enhanced mitophagy in vivo and in vitro. Moreover, numbers of mitophagosomes were increased in optic nerves of PR-619-treated ocular hypertensive rats in vivo. Furthermore, parkin knockdown negated the salutary effects of PR-619 and attenuated expression of parkin-dependent mitophagy effectors in RGCs subjected to glutamate excitotoxicity in vitro. Collectively, these findings implicate augmented parkin-mediated mitophagy as the mechanistic substrate underscoring the neuroprotective capacity of PR-619 in experimental glaucoma. These revelations engender the prospect that pharmacological agents or biotherapeutics augmenting parkin-mediated mitophagy may proffer viable therapeutic modalities for glaucomatous neurodegeneration characterized by impaired mitophagy.

Abstract Background Greater yam is a key staple crop grown in tropical and subtropical regions, while its asexual propagation mode had led to non-flowering mutations. How transposable elements contribute to its genetic variations is rarely analyzed. We used transcriptome and whole genome sequencing data to identify active transposable elements (TEs) and genetic variation caused by these active TEs. Our aim was to shed light on which TEs would lead to its intraspecies variation. Results Annotation of de novo assembly transcripts indicated that 0.8 − 0.9% of transcripts were TE related, with LTR retrotransposons (LTR-RTs) accounted for 65% TE transcripts. A large portion of these transcripts were non-autonomous TEs, which had incomplete functional domains. The majority of mapped transcripts were distributed in genic deficient regions, with 9% of TEs overlapping with genic regions. Moreover, over 90% TE transcripts exhibited low expression levels and insufficient reads coverage to support full-length structure assembly. Subfamily analysis of Copia and Gypsy, the two LTR-RTs revealed that a small number of subfamilies contained a significantly larger number of members, which play a key role in generating TE transcript. Based on resequencing data, 15,002 L-RT insertion loci were detected for active LTR-RT members. The insertion loci of LTR-RTs were highly divergent among greater yam accessions. Conclusions This study showed the ongoing transcription and transpositions of TEs in greater yam, despite low transcription levels and incomplete proteins insufficient for autonomous transposition. While our research did not directly link these TEs to specific yam traits such as tuber yield and propagation mode, it lays a crucial foundation for further research on how these TE insertion polymorphisms (TIPs) might be related to variations in greater yam traits and its tuber propagation mode. Future research may explore the potential roles of TEs in trait variations, such as tuber yield and stress resistance, in greater yam.

Abstract There is a growing interest in the creation of engineered condensates formed via liquid–liquid phase separation (LLPS) to exert precise cellular control in prokaryotes. However, de novo design of cellular condensates to control metabolic flux or protein translation remains a challenge. Here, we present a synthetic condensate platform, generated through the incorporation of artificial, disordered proteins to realize specific functions in Bacillus subtilis. To achieve this, the “stacking blocks” strategy is developed to rationally design a series of LLPS-promoting proteins for programming condensates. Through the targeted recruitment of biomolecules, our investigation demonstrates that cellular condensates effectively sequester biosynthetic pathways. We successfully harness this capability to enhance the biosynthesis of 2’-fucosyllactose by 123.3%. Furthermore, we find that condensates can enhance the translation specificity of tailored enzyme fourfold, and can increase N-acetylmannosamine titer by 75.0%. Collectively, these results lay the foundation for the design of engineered condensates endowed with multifunctional capacities.

The traditional quaternion is used as the description parameter of the nonlinear state model of the aircraft, and the accuracy of the attitude estimation is presented. A square root cubature Kalman filter algorithm based on quaternion is proposed. The algorithm takes the attitude quaternion error and the gyro drift error as the state quantity, and measures the attitude quaternion of SINS/SLAM navigation. The square root cubature Kalman filter algorithm is used for pose estimation, which not only solves the standardization problem of traditional quaternion, but also reduces the state dimension and complexity of the square root UKF algorithm of traditional quaternion, and improves the numerical stability.

Abstract Objective This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis. Method PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis. Results A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia. Conclusion Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia. PROSPERO registration number CRD42023472974.

Abstract Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study in hens with distinct egg production, to detect the hub candidate genes and construct hub molecular networks contributing to egg-laying phenotypic differences. We identifiy three hub candidate genes as egg-laying facilitators: TFPI2, which promotes the GnRH secretion in hypothalamic neuron cells; CAMK2D, which promotes the FSHβ and LHβ secretion in pituitary cells; and OSTN, which promotes granulosa cell proliferation and the synthesis of sex steroid hormones. We reveal key endocrine factors involving egg production by inter-tissue crosstalk analysis, and demonstrate that both a hepatokine, APOA4, and an adipokine, ANGPTL2, could increase egg production by inter-tissue communication with hypothalamic-pituitary-ovarian axis. Together, These results reveal the molecular mechanisms of multi-tissue coordinative regulation of chicken egg-laying performance and provide key insights to avian reproductive regulation.

Abstract Background Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. Methods We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. Results Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. Conclusion Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

Abstract Background Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon’s experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention. Methods A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2. Results 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC. Conclusions High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk.

Abstract This paper investigated the global attractive set for quaternion-valued neural networks (QVNNs) with leakage delay, time-varying delay, and neutral items. Based on various basic conditions of activation function, the global attractive set and global exponential attractive set of QVNNs are given combined with novel analytical techniques and Lyapunov theory. The QVNNs are studied by a direct method, without any decomposition. The time delay can be non-differential, which makes the results more pragmatic. Restrictions on the activation function of the neutral item are relaxed. The neutral activation function can be bounded or unbounded, which makes the results more practical. Two simulation examples are given to verify the validity of the theory results.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin β1 expression. Subsequently, integrin β1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Abstract Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens.

The deintercalation of weakly bonded A element affects the microstructure and properties of MAX phases and their reinforced composites. In this work, the effect of M-site element on the interaction of Al-containing M2AlC (M = V, Cr) phase and Ag, and the induced properties of Ag/M2AlC electrical contact materials (ECMs) were investigated. Though Ag and Al are soluble to each other and can form intermetallics, the variation of M element significantly affected the vacancy formation of Al, and thereby the interfacial reaction of Ag/M2AlC. The difficult formation of Al vacancy in V2AlC contributed to no obvious interfacial reaction in Ag/V2AlC. But the easy deintercalation of Al atoms in Cr2AlC led to their massive replacement by Ag, which generated Ag nano-twins and Cr3C2 with the same crystallographic relationship in one original Cr2AlC, and Cr7C3 and Ag3Al as well. Due to the distinct interactions, the resistivities of Ag/V2AlC and Ag/Cr2AlC increased by roughly 1 and 5 times after sintering, respectively. The low resistivity and proper hardness of the sintered Ag/V2AlC, which were very close to those of the “all-purpose” commercial Ag/CdO, contributed to its superior arc erosion resistance.

The prediction of mine water inflow is of great significance to the safe production of coal mines. The accurate selection of hydrogeological parameters and the selection of calculation methods have a great influence on the accurate prediction of mine water inflow. At the same time, taking into account the actual mining of the mine, the water inflow is not stable from the early stage of mining, but dynamic. In order to improve the accuracy of water inflow prediction and better serve coal mining, based on the analysis of geological and hydrogeological conditions of Donggou Coal Mine in Xinjiang and the selection of accurate hydrogeological parameters, two water inflow prediction methods suitable for Donggou Coal Mine were selected for comparative analysis. The calculation results show that : ① The water inflow calculated by the unsteady flow water release-section flow method shows dynamic change characteristics. After the mining intensity is stable, the change range becomes smaller and finally tends to be stable. ② The predicted water inflow calculated by the large well method and the unsteady flow water release-section flow method is 3396 m3/d, 599.87 − 612.9 m3/d and the actual water inflow 480 m3/d, respectively. The difference with the actual value is in ascending order of magnitude 607.5% > 24.97% − 27.69% ; ③ According to the verification and analysis of the water inflow data generated by the actual mining of the mine, the water inflow calculated by the unsteady flow water release-section flow method is basically consistent with the water inflow generated by the actual mining. The accuracy of the water inflow prediction results is in the order of unsteady flow water release-section flow method > large well method ; ④ In the case of sufficient data and accurate parameters, it is recommended to give priority to the unsteady flow release-section flow method to calculate the water inflow. It is recommended to use the large well method first under the condition that the water supply boundary conditions are poor and meet the requirements of the large well method. On the one hand, the calculation results fully verify the accuracy of the unsteady flow release-section flow method. On the other hand, it provides a reference for the calculation of water inflow in coal mines, and also provides data support for the safe production of Donggou Coal Mine.

Abstract Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.

Abstract Background Apoptotic cell‐conditioned mesenchymal stem cells (AC‐MSCs) exhibit stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2); however, whether AC‐MSCs exhibit enhanced therapeutic effects on systemic lupus erythematosus (SLE) remains unknown. Methods Splenocytes from MRL/MPJ‐Faslpr (MRL/lpr) mice were cocultured with AC‐MSCs, and the proportion of plasma cells was determined by flow cytometry. MSCs, AC‐MSCs, COX2 knockdown MSCs, and COX2 knockdown AC‐MSCs were infused into MRL/lpr mice (n = 10/group). Survival rates and lupus symptoms, including proteinuria, kidney injury, renal immune complex deposition, and autoantibody production, were assessed. Additionally, the number of plasma cells and serum levels of inflammatory cytokines were measured. Results The AC‐MSCs significantly inhibited plasma cells via PGE2 after 24 h coculture in vitro, whereas MSCs did not. In the MRL/lpr mice, AC‐MSC treatment led to a significantly higher survival rate than phosphate‐buffered saline (PBS) treatment (90% vs. 50%, p

Abstract The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2 –•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2 –• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

Abstract The most extraordinary systems of symbiosis in insects are found in the suborder Auchenorrhyncha of Hemiptera, which provide unique perspectives for uncovering complicated insect-microbe symbiosis. We investigated symbionts associated with bacteriomes and fat bodies in six cicada species, and compared transmitted cell number ratio of related symbionts in ovaries among species. We reveal that Sulcia and Hodgkinia or a yeast-like fungal symbiont (YLS) are segregated from other host tissues by the bacteriomes in the nymphal stage, then some of them may migrate to other organs (i.e., fat bodies and ovaries) during host development. Particularly, YLS resides together with Sulcia in the “symbiont ball” of each egg and the bacteriomes of young-instar nymphs, but finally migrates to the fat bodies of adults in the majority of Hodgkinia-free cicadas, whereas it resides in both bacteriome sheath and fat bodies of adults in a few other species. The transmitted Sulcia/YLS or Sulcia/Hodgkinia cell number ratio in ovaries varies significantly among species, which could be related to the distribution and/or lineage splitting of symbiont(s). Rickettsia localizes to the nuclei of bacteriomes and fat bodies in some species, but it was not observed to be transmitted to the ovaries, indicating that this symbiont may be acquired from environments or from father to offspring. The considerable difference in the transovarial transmission process of symbionts suggests that cellular mechanisms underlying the symbiont transmission are complex. Our results may provide novel insights into insect-microbe symbiosis.

Atrazine (ATR) is a broad-spectrum herbicide with dopaminergic (DAergic) neurotoxicity that can cause Parkinson’s disease (PD)-like syndrome. However, research on preventing ATR neurotoxicity is unclear. Soybean isoflavones (SI) are natural plant compounds with neuroprotective effects. In this study, we found that pre-administration of SI prevented ATR-induced motor dysfunction and substantia nigra pathological damage. RNA-seq datasets revealed that the neuroprotective effect of SI was related to autophagy. Further experiments showed that ATR inhibited autophagy, and SI pre-administration before ATR exposure increased autophagy. In addition, single-cell data analysis combined with experimental verification showed that the gene VPS13A was a key target by which SI protected DAergic neurons from ATR damage, and inhibiting VPS13A-induced autophagy was a key mechanism enabling SI prevention of neuron damage. Together, these findings provide new insights for the development of preventive measures and intervention targets protecting against functional neuronal damage caused by ATR and other herbicides.

4′,5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia. 4′,5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo. These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1.

BackgroundA substantial amount of research has explored the intricate relationship between exercise and sleep quality, consistently confirming that exercise can effectively enhance sleep quality. Nevertheless, previous studies have yet to conclusively determine which specific exercise program is most efficacious in improving sleep quality. To address this gap, the present study systematically evaluated the differential effects of various types of exercise, as well as exercise dosages (including duration, intervention period, frequency, and intensity), on sleep outcomes using a network meta-analysis approach. This endeavor aims to provide evidence-based support for the development of scientifically effective exercise programs tailored to improve sleep quality.MethodsThrough the Web of Science, PubMed, Cochrane Library, Embase, and Scopus databases, we conducted a search for randomized controlled trials investigating the effects of exercise interventions on sleep, with a search cutoff date of April 30, 2024. We rigorously selected the literature according to the PICOS principle, and two independent researchers extracted the data. We would like to change this passage to: Bias risk assessment was conducted using the RevMan 5.4 software, and traditional meta-analysis and network meta-analysis were performed using Stata 17.0 software to generate forest plots, network evidence plots, and funnel plots. Furthermore, we adopted the surface under the cumulative ranking curve (SUCRA) to evaluate and rank the intervention effects of different exercise types and dosages on sleep quality. To verify the robustness of our study results, we performed a sensitivity analysis using the leave-one-out method.ResultsThe study strictly adhered to the PRISMA guidelines and included 58 RCT papers with a total of 5,008 participants. The network meta-analysis revealed significant variations in the impact of exercise frequency on sleep outcomes when compared to the control group. Interventions of 1–2 times per week [SMD = −0.85, 95% CI (−1.43, −0.26)], 3 times per week [SMD = −0.45, 95% CI (−0.80, −0.11)], and 4 times per week [SMD = −1.09, 95% CI (−1.92, −0.26)] demonstrated the most notable effects. Interventions lasting ≤30 min and 60–65 min were significantly more effective than the control group, with ≤30 min proving significantly more effective than 40–55 min [SMD = 0.75, 95% CI (0.01, 1.49)]. Interventions lasting 9–10 weeks [SMD = −1.40, 95% CI (−2.37, −0.44)], 12–16 weeks [SMD = −0.55, 95% CI (−0.90, −0.20)], and ≥ 24 weeks [SMD = −0.71, 95% CI (−1.31, −0.10)] were all significantly more effective than the control group. Additionally, the 9–10 weeks intervention period was found to be significantly more effective than the 6–8 weeks period [SMD = −1.21, 95% CI (−2.37, −0.04)]. Furthermore, interventions of moderate intensity [SMD = −1.06, 95% CI (−1.52, −0.61)] and high intensity [SMD = −1.48, 95% CI (−2.55, −0.40)] exercise interventions yielded significantly greater benefits compared to the control group. Specifically, high intensity interventions [SMD = −1.97, 95% CI (−3.37, −0.56)] and moderate intensity [SMD = −1.55, 95% CI (−2.57, −0.54)] exercise interventions were found to be significantly more effective than moderate-high intensity interventions. In terms of exercise types, aerobic exercise [SMD = −0.56, 95% CI (−0.86, −0.27)], traditional Chinese exercises [SMD = −0.57, 95% CI (−0.97, −0.18)], and combined exercise [SMD = −0.99, 95% CI (−1.66, −0.32)] interventions all produced significant improvements compared to the control group. The study determined that the most effective combination of exercise prescription elements for enhancing sleep quality includes a frequency of 4 times per week (SUCRA = 84.7), a duration of ≤30 min (SUCRA = 92.2), a period of 9–10 weeks (SUCRA = 89.9), and high-intensity (SUCRA = 92.9) combined exercise (SUCRA = 82.7).ConclusionThe current evidence indicates that combined exercise with a frequency of 4 times per week, a duration of ≤30 min, a period of 9–10 weeks, and high intensity is most effective for improving sleep quality. Nevertheless, due to the limited number of studies included, further research is needed to enhance the reliability of the findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024555428.

Oral verrucous carcinoma (OVC) and proliferative verrucous leukoplakia (PVL) share similar histological characteristics and may have a common origin. When they appear simultaneously, the risk of malignant transformation in PVL increases. In elderly patients with both conditions, a safe, effective, simple, and minimally invasive treatment is preferable. Photodynamic therapy (PDT), a non-invasive treatment, utilizes specific wavelengths of light to activate photosensitizers, generating reactive oxygen species that selectively target malignant tissues with cytotoxic effects. This case report describes an elderly patient with coexisting extensive leukoplakia, PVL, and OVC, who achieved complete remission with no recurrence at 10 months following PDT. The treatment resulted in a satisfactory clinical outcome, preserving both the appearance and function of the oral cavity.

ABSTRACT: Pekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.

Food provides essential nutrients and energy for wildlife and directly influences the compositional patterns of the gut microbiota in natural reservoirs. Little is known about the interspecific differences and correlations between diet and microbial communities in sympatric herbivores. We conducted chloroplast trnL and 16S rRNA genes amplicon sequencing of 90 faecal samples from sika deer (Cervus nippon kopschi), Reeve’s muntjac (Muntiacus reevesi), and a Chinese hare (Lepus sinensis). Diet analysis revealed that sika deer predominantly foraged on Rubus (36.5 %), Loropetalum (25.5 %), and Eurya (13.4 %) at the genus level; Reeve’s muntjac favoured Rubus (51.8 %), Eurya (11.0 %), and Euonymus (6.1 %); Chinese hare showed dominance in Rubus (15.8 %), Smilax (15.6 %), and Rhus (10.6 %) consumption, with all these forage plants being shrubs. The gut microbiota of the three herbivores was characterised by Firmicutes, Bacteroidetes, and Proteobacteria, although the relative abundances of these taxa differed across herbivore species. Alpha diversity indicated no significant differences between sika deer and Reeve’s muntjac, whereas alpha indices showed significant differences between sika deer and Chinese hare (p < 0.05). Beta diversity analysis indicated significant differences between the Chinese hare and sika deer, as well as between the Chinese hare and Reeve’s muntjac (p < 0.05), with no significant difference found between the two cervid species, which may be attributed to the influence of interspecific genetics and evolutionary factors. Due to seasonal shifts, the food availability for herbivores decreased, resulting in the convergent adaptation of shrubs consumed by the three species. Furthermore, PICRUSt functional profile prediction indicated that the gut microbiota of the three species were mainly enriched in metabolic functions. Mantel correlation analysis suggested that the gut microbiota of sika deer showed a significant positive correlation with five genera of plants, one genus of Reeve’s muntjacs, and three genera of Chinese hare (p < 0.01), suggesting that the gut microbiota of sika deer may be more susceptible to changes in food abundance. Our study emphasises how the winter climate affects the foraging strategies and microbial communities of the three herbivores, as well as their correlations. These results may further contribute to the food selection, regulation of gut microbiota, disease prevention, conservation, and management of sika deer and other sympatric herbivores.

Abstract We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

Abstract Introduction The aim of this work is to investigate the dynamic changes of capsular-intraocular lens (IOL) adhesion in plate-haptic hydrophilic and loop-haptic hydrophobic eyes. Methods Cataract eyes that met the inclusion criteria were randomly assigned to receive implantation of a plate-haptic hydrophilic or loop-haptic IOL. The anterior capsular adhesion, posterior capsular adhesion, and the configurations of the capsular bend were evaluated using swept-source optical coherence tomography at 1 day, 1 week, 1 month, and 3 months postoperatively. Results In total, 66 eyes of 66 patients were eligible for the analysis: 33 in the plate-haptic group and 33 in the loop-haptic group. The contact between the anterior capsule and IOL in the plate-haptic group was earlier than that in the loop-haptic group upon comparing the measurements taken at 1 day and 1 week (p = 0.001, p = 0.003, respectively). The complete attachment of the posterior capsule and IOL in the plate-haptic group was significantly greater at 1 week, 1 month, and 3 months (p = 0.001, p = 0.000, p = 0.001, respectively). The capsular bend index of the plate-haptic group was significantly greater than that of the loop-haptic group at each time points except at 1 day (p = 0.007, p = 0.049, p = 0.005, respectively). Furthermore, a new type of capsular bend, “cocked adhesion,” was observed in the plate-haptic eyes. Conclusions The plate-haptic IOL demonstrated excellent capsular adhesion compared to the loop-haptic IOL, which was probably attributed to haptic compressibility. A special cocked configuration of the capsular bend in plate-haptic IOL was observed for the first time. Further studies are warranted to confirm the effect of the new type of capsular bend.

Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

Abstract Background The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). Methods In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. Results The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). Conclusion The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

Abstract Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Abstract Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

In order to overcome the problems existed in the construction process of complex giant system of smart mine, the overall technical framework of smart mine construction was proposed, and a detailed description was made from the aspects of smart mine system model construction, underground space reconstruction and model dynamic update, machine vision measurement technology, radio frequency explosion-proof test method of gas environment, mine safety closed-loop control system, smart mine standard system, etc. The smart mine was divided into information sensing support layer, edge computing layer, cloud data center, multi-type network, intelligent mine production management and control platform, intelligent mine production system and intelligent mine operation and maintenance management system. The smart mine technology architecture based on the deep integration of multiple systems was built. Based on the knowledge map and information extraction of smart mine, a smart mine system model driven by data innovation, based on communication network and centered on data computing power was constructed. A 3D visual space model based on machine vision perception information and supplemented by other perception information was constructed, and a 3D vision and spatial reconstruction framework of mine underground scene was proposed to realize the reconstruction and dynamic update of the 3D space of underground mine. Based on machine vision technology, the identification algorithm of downhole equipment position and coal-rock interface was developed to realize the simultaneous aerial measurement of fully mechanized mining equipment group and coal-rock interface. The limitations and shortcomings of the current explosion-proof standards on the power of 5G base stations in the underground gas environment were discussed, and a special test device for radio-frequency electromagnetic energy explosion-proof was designed and developed, which provides a method for reference to improve the power threshold of underground 5G base stations. The technical framework of mine disaster closed-loop management and control system, which integrates comprehensive perception of disaster information, independent decision-making of prevention and control plan, and coordinated control of prevention and control equipment, was proposed to realize advanced prediction and early warning and coordinated prevention and control of underground disasters. The framework of intelligent coal mine standard system was constructed, the typical cases of intelligent construction of coal mine and metal mine in China were analyzed, and the development trend and suggestions of intelligent mine construction were put forward.

Abstract Background Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is essential to reduce its consequences. This study was aimed at determining the activities of new‐onset primary Sjögren syndrome (pSS) since the emergence of SARS‐CoV‐2. Methods This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group (n = 24) or vaccinated and infected group based on exposure (n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS‐CoV‐2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS‐CoV‐2 were assigned to a vaccinated and infected group. The controls comprised age‐ and sex‐matched patients who had not been exposed to SARS‐CoV‐2 before December 2019 (n = 21). We then compared data among the three groups. Results The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti‐nuclear antibody (ANA) titers > 1:320 (n = 12; 50%) and anti‐phospholipid antibodies (aPL) (n = 7; 29%) than the controls. The frequency of anti‐Ro/SSA antibodies (13, 65%), ANA titers > 1:320 (n = 16; 80%), and aPLs (n = 7; 29%) (n = 5; 25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups (p

The effects of equal channel angular pressing (ECAP), multiple cryogenic rolling and aging treatment on the microstructure, mechanical properties, and electrical conductivity of Cu–1Cr–0.1Zr alloy were investigated. The results showed that multi-stage deformation and aging (ECAP at ambient temperature + primary cryogenic rolling 50 % + 450 °C aging for 1h + secondary cryogenic rolling 80 % + 150 °C aging for 1h) can lead to the rational comprehensive performance of Cu–1Cr–0.1Zr alloy with tensile strength of 730 MPa and electrical conductivity of 75.5 % IACS. The microstructure characterization revealed that in the Cu–1Cr–0.1Zr alloy a subject to the multistage deformation and aging, there ultrafine grains, nanotwins, nanoprecipitates and micrometer precipitates constituted the nanostructured state. The increase in tensile strength was mainly attributed to fine grain strengthening and precipitation strengthening, followed by dislocation strengthening due to low temperature deformation. The ECAP resulted in the refinement of grain, and the increased dislocation density. The following primary cryogenic rolling refined the grains up to ultrafine-grained (UFG) size and created nanotwins. The introduction of nano-precipitated phases by intermediate aging pinned dislocations and impeded the motion of dislocation entanglements, allowing the alloy to achieve higher strength. Multi-stage deformation and aging resulted in a higher density of twin boundaries in the nanostructure and dilute solid solution in comparison with one stage treatment. These microstructural features were responsible for the excellent electrical conductivity.

PurposeThis study aimed to evaluate the optical coherence tomography angiography (OCTA) changes in subzones of peripapillary atrophy (PPA) among type 2 diabetic patients (T2DM) with or without diabetic retinopathy (DR) using well-designed deep learning models.MethodsA multi-task joint deep-learning model was trained and validated on 2,820 images to automate the determination and quantification of the microstructure and corresponding microcirculation of beta zone and gamma zone PPA. This model was then applied in the cross-sectional study encompassing 44 eyes affected by non-proliferative diabetic retinopathy (NPDR) and 46 eyes without DR (NDR). OCTA was utilized to image the peripapillary area in four layers: superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary (CC) and middle-to-large choroidal vessel (MLCV).ResultsThe patients in both groups were matched for age, sex, BMI, and axial length. The width and area of the gamma zone were significantly smaller in NPDR group compared to the NDR group. Multiple linear regression analysis revealed a negative association between the diagnosis of DR and the width and area of the gamma zone. The gamma zone exhibited higher SCP, DCP and MLCV density than the beta zone, while the beta zone showed higher CC density than the gamma zone. In comparison to the NDR group, the MLCV density of gamma zone was significantly lower in NPDR group, and this density was positively correlated with the width and area of the gamma zone.DiscussionDR-induced peripapillary vascular changes primarily occur in gamma zone PPA. After eliminating the influence of axial length, our study demonstrated a negative correlation between DR and the gamma zone PPA. Longitudinal studies are required to further elucidate the role of the gamma zone in the development and progression of DR.

This study investigated influences of faba bean (Vicia faba L.) supplementary diet (VFSD) on tilapia muscle texture through muscle-gut axis. Tilapia were fed diets with varying VSFD contents for 60 days. Results indicated no significantly growth changes across groups. However, VFSD increased muscle hardness and chewiness, with higher collagen deposition between muscle fibers. Transcriptome revealed an increase in differentially-expressed genes (DEGs) related to myofibril component and TGF-β, MAPK, FOXO, insulin pathways. Crucial DEGs among interaction network between these pathways, including foxo3, mitf, smad1, smad7, and flt1, were validated via qPCR. Gut microbiota analysis showed VFSD decreased Pseudomonas, Ralstonia, and Aurantimicrobium abundance, while increased Rhodobacter, Akkermansia, and Propionibacteriaceae, which significantly impacting quorum sensing and ABC transporters. Microbiota variation highly correlated with muscle DEGs, suggesting a link between muscle phenotype and gut microbiota. In summary, VFSD alters meat texture by influencing collagen deposition and myofibril reconstruction, which may be regulated by LPS- and ROS-related pathways through altering the composition of the microbial community.

This study investigated the effects of adding various concentrations of cholesterol and soy lecithin to feed on the growth performance, physiology, biochemistry, and serum metabolomics of Cyprinus carpio var. Two cholesterol concentrations (1 % and 2 %) and four soy lecithin concentrations (0 %, 2 %, 4 %, and 6 %) were employed, resulting in eight experimental groups (C1S0, C1S2, C1S4, C1S6, C2S0, C2S2, C2S4, and C2S6) that were cultivated for 60 days. The addition of C2S2 to the feeds enhanced the growth (WGR and SGR), antioxidant capacity (CAT, SOD, MDA, T-AOC, and GSH-Px), and lipid metabolism (TG, LDL-C, HDL-C, LPL, and HL) in C. carpio var. A significant interaction (P < 0.05) was observed between cholesterol and soy lecithin concentrations for WGR, SGR, and FCR, and a highly significant interaction (P < 0.01) was observed for CAT, SOD, T-AOC, GSH-Px, TG, LDL-C, and HDL-C in C. carpio var. Based on these results, three comparisons (C1S4-vs-C1S0, C2S2-vs-C2S0, and C2S2-vs-C1S2) were selected to analyze the serum metabolic profiles of C. carpio var. through LC-MS. The differential metabolites screened included amino acids and their metabolites, nucleotides and their metabolites, bile acids, fatty acids, carbohydrates and their metabolites. The metabolic pathways involved were purine metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and ABC transporter proteins. In summary, the interaction between cholesterol and soy lecithin significantly influenced the growth performance, antioxidant capacity, and cholesterol metabolism of C. carpio var. The most beneficial effects on growth and lipid metabolism were observed when both cholesterol and soy lecithin were added at a concentration of 2 %. The present study provides theoretical guidance for the appropriate concentrations of cholesterol and lecithin in aquafeeds.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as “unhealthy macrophages”. Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Summary: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4+ T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-β) plus IL-4 activates pSmad3-Ser213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-β-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc.

BackgroundThe objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy.MethodsA comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria.ResultsA total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18–0.41, p

In recent years, porcine diarrhea-associated viruses have caused significant economic losses globally. These viruses present similar clinical symptoms, such as watery diarrhea, dehydration, and vomiting. Co-infections with porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are common. For the rapid and on-site preliminary diagnosis on the pig farms, this study aimed to develop a colloidal gold immunochromatography assay (GICA) strip for the detection of PEDV and TGEV simultaneously. The GICA kit showed that there was no cross-reactivity with the other five common porcine viruses. With visual observation, the lower limits were approximately 104 TCID50/mL and 104 TCID50/mL for PEDV and TGEV, respectively. The GICA strip could be stored at 4°C or 25°C for 12 months without affecting its efficacy. To validate the GICA strip, 121 clinical samples were tested. The positive rates of PEDV and TGEV were 42.9 and 9.9%, respectively, and the co-infection rate of the two viruses was 5.8% based on the duplex GICA strip. Thus, the established GICA strip is a rapid, specific, and stable tool for on-site preliminary diagnosis of PEDV- and TGEV-associated diarrhea.

Fungal biofilm is a microbial community composed of fungal cells and extracellular polymeric substances (EPS). In recent years, fungal biofilms have played an increasingly important role in many fields. However, there are few studies on fungal biofilms and their related applications and development are still far from enough. Therefore, this review summarizes the composition and function of EPS in fungal biofilms, and improves and refines the formation process of fungal biofilms according to the latest viewpoints. Moreover, based on the study of Saccharomyces cerevisiae and Candida albicans, this review summarizes the gene regulation network of fungal biofilm synthesis, which is crucial for systematically understanding the molecular mechanism of fungal biofilm formation. It is of great significance to further develop effective methods at the molecular level to control harmful biofilms or enhance and regulate the formation of beneficial biofilms. Finally, the quorum sensing factors and mixed biofilms formed by fungi in the current research of fungal biofilms are summarized. These results will help to deepen the understanding of the formation process and internal regulation mechanism of fungal biofilm, provide reference for the study of EPS composition and structure, formation, regulation, group behavior and mixed biofilm formation of other fungal biofilms, and provide strategies and theoretical basis for the control, development and utilization of fungal biofilms.

Background Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases. Objectives To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors. Methods TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide 131 I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and 131 I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by 131 I-labeled Atezolizumab and IgG in-vitro distribution. Results Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of 131 I-labeled IgG was higher than that of 131 I-labeled Atezolizumab at any time point. Conclusion Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Abstract Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE‐like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H+‐ATPase (v‐ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v‐ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v‐ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases.

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID‐19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.