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Currently, the phylogenetic relationships of Tragopogon pratensis Linnaeus (1753) remain unclear. This study presents the first report on the complete chloroplast genome of T. pratensis, which is a quadripartite structure with a length of 153,002 bp and containing a large single copy (LSC, 84,225 bp) region, a small single copy (SSC, 18,407 bp) region, a pair of inverted repeats (IR, 25,185 bp) regions. A total of 134 genes are identified, including 87 protein-coding genes, 8 rRNA genes, 37 tRNA genes, and 2 pseudogenes. Phylogenetic analysis revealed that T. pratensis is most closely related to T. dubius and that Tragopogon is a monophyletic genus.

Abstract The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.

Abstract Objective This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). Methods In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. Results Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3–4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. Conclusions Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Abstract Background The incidence of cervical spinal brucellosis is low, only a few case reports have been published, and case series are not widely reported in the medical literature. Therefore, clinical features, management, and outcomes of cervical spinal brucellosis are relatively unknown. In this series, the authors report 15 cases of patients with cervical spinal brucellosis, including clinical characteristic, imaging findings, management plans, the institution’s experience, and outcomes at 1 year postoperatively. Methods The study reviewed the clinical and radiographic records of 15 patients who received antimicrobial pharmacotherapy, and anterior cervical debridement and fusion for cervical spinal brucellosis. The data collected included patient demographic characteristics, spinal level affected, abscess, neurology, pathological reports, duration and type of antimicrobial regimens, details of orthopedic management, and complications incurred during the procedure. Results Neck pain (100%) and limb paralysis (86.7%) were the most common clinical presentations, and the disease had a rapid progression. The C6-7 segment was the most commonly affected segment, followed by C4-5 and C5-6. Imaging commonly revealed epidural or paravertebral abscesses (80%). There was a significant improvement in the VAS, JOA, and NDI scores three months after surgery, and the scores continued to improve until the final follow-up. There was a statistically significant difference between the pre- and postoperative scores (P

Abstract Background Cartilage is a kind of avascular tissue, and it is difficult to repair itself when it is damaged. In this study, we investigated the regulation of chondrogenic differentiation and vascular formation in human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) by the long-chain noncoding RNA small nucleolar RNA host gene 1 (SNHG1) during cartilage tissue regeneration. Methods JBMMSCs were isolated from the jaws via the adherent method. The effects of lncRNA SNHG1 on the chondrogenic differentiation of JBMMSCs in vitro were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Pellet experiment, Alcian blue staining, Masson’s trichrome staining, and modified Sirius red staining. RT-qPCR, matrix gel tube formation, and coculture experiments were used to determine the effect of lncRNA SNHG1 on the angiogenesis in JBMMSCs in vitro. A model of knee cartilage defects in New Zealand rabbits and a model of subcutaneous matrix rubber suppositories in nude mice were constructed for in vivo experiments. Changes in mitochondrial function were detected via RT-qPCR, dihydroethidium (DHE) staining, MitoSOX staining, tetramethyl rhodamine methyl ester (TMRM) staining, and adenosine triphosphate (ATP) detection. Western blotting was used to detect the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). Results Alcian blue staining, Masson’s trichrome staining, and modified Sirius Red staining showed that lncRNA SNHG1 promoted chondrogenic differentiation. The lncRNA SNHG1 promoted angiogenesis in vitro and the formation of microvessels in vivo. The lncRNA SNHG1 promoted the repair and regeneration of rabbit knee cartilage tissue. Western blot and alcian blue staining showed that the JAK inhibitor reduced the increase of STAT3 phosphorylation level and staining deepening caused by SNHG1. Mitochondrial correlation analysis revealed that the lncRNA SNHG1 led to a decrease in reactive oxygen species (ROS) levels, an increase in mitochondrial membrane potential and an increase in ATP levels. Alcian blue staining showed that the ROS inhibitor significantly alleviated the decrease in blue fluorescence caused by SNHG1 knockdown. Conclusions The lncRNA SNHG1 promotes chondrogenic differentiation and angiogenesis of JBMMSCs. The lncRNA SNHG1 regulates the phosphorylation of STAT3, reduces the level of ROS, regulates mitochondrial energy metabolism, and ultimately promotes cartilage regeneration.

Avoiding the upward-bending hook is a highly pressing and challenging task in the field of similar aluminum alloys friction stir lap welding (FSLW). To enhance formation quality and then obtain the welded lap joint with high tensile shear load, a novel impacting flow FSLW (IF-FSLW) process based on the X-shape reverse-threaded pin was proposed in this study. Three welding tools with different tool geometry parameters were developed to analyze how the locations of the materials accumulated zone (MAZ) influenced the joint formation and the joint loading capacity, and 7B04 aluminum alloys were chosen as research subject. Results showed that the horizontally-impacting and vertically-impacting effects of MAZ on and above the original lap interface made the hook respectively present the forky structure at the end and the downward-bending morphology, and the horizontally-impacting effect of MAZ made the stir zone (SZ) have a protruding morphology near the MAZ. Under the tensile fracture mode, the IF-FSLW joint under configuration A had a greatly heightened tensile shear load under the combined actions of the downward-bending hook and the enlarged SZ. The tensile shear load of IF-FSLW joint reached 8.62 kN/mm under the reasonable combination of tool geometry parameters and welding process parameters. The IF-FSLW process by the X-shape reverse-threaded pin provides an effective way to obtain a superb-strength lap joint of aluminum alloys.

Abstract Background It is well established that hypercholesterolemia increases the risk of atherosclerosis, especially because it reduces the availability of nitric oxide (NO). However, the relationship between hypercholesterolemia and NO in regulating colorectal cancer development and progression remains unknown. Methods We conducted bioinformatics analysis, qRT-PCR, ChIP-qPCR assays, luciferase report assays, clonogenic survival assays, and multiple mouse models to investigate the function and mechanism of hypercholesterolemia in regulating NO signaling. Additionally, NOS inhibitors were used to evaluate the potential of therapeutic strategy in anti-tumor response. Results Here, we show that oxidized low-density lipoprotein (oxLDL) cholesterol and its receptor LOX-1 are essential for hypercholesterolemia-induced colorectal tumorigenesis. Mechanically, the oxLDL promotes the oxidant stress-dependent induction of hypoxia signaling to transcriptionally up-regulate NO synthase (NOS) especially NOS1 expression in colorectal cancer (CRC) cells. More importantly, our results suggested that selective inhibition of NOS1 with its specific inhibitor Nω-Propyl-L-arginine is a suitable therapeutic strategy for hypercholesterolemia-related CRC with both efficacy and toxicity reduction. Conclusions Our findings established that hypercholesterolemia induces the oxidant stress-dependent induction of hypoxia signaling to transcriptionally up-regulate NOS1 expression in CRC cells, and the clinically applicable NOS1 inhibitor Nω-Propyl-L-arginine represents an effective therapeutic strategy for hypercholesterolemia-related CRC.

Abstract The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint–liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Peanut (Arachis hypogaea L.) is a globally important oil crop. Web blotch is one of the most important foliar diseases affecting peanut, which results in serious yield losses worldwide. Breeding web blotch-resistant peanut varieties is the most effective and economically viable method for minimizing yield losses due to web blotch. In the current study, a bulked segregant analysis with next-generation sequencing was used to analyze an F2:3 segregating population and identify candidate loci related to web blotch resistance. Based on the fine-mapping of the candidate genomic interval using kompetitive allele-specific PCR (KASP) markers, we identified a novel web blotch resistance-related locus spanning approximately 169 kb on chromosome 16. This region included four annotated genes, of which only Arahy.35VVQ3 had a non-synonymous single nucleotide polymorphism in the coding region between the two parents. Two markers (Chr.16.12872635 and Chr.16.12966357) linked to this gene were shown to be co-segregated with the resistance of peanut web blotch by 72 randomly selected recombinant inbred lines (RIL), which could be used in marker-assisted breeding of resistant peanut varieties.

The essential oil of Artemisia annua grown in the Beijing area was extracted by hydrodistillation, and then its volatile components were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vitro antioxidant activity of the Artemisia annua essential oil was determined by measuring the scavenging rate of DPPH and hydroxyl radicals, its antibacterial activity by using the agar diffusion method, and its toxicological properties by perfusing mice with different doses of the essential oil. The results showed that the extraction rate of the Artemisia annua essential oil was 1.04‰, with 332 essential oil components being identified by GC-MS analysis. Of these, 22 components accounted for 71.09% of the total volatiles, with relatively high contents of artemisinone (19.34%) and (+)-α-pinene (6.10%). The Artemisia annua essential oil exhibited good scavenging activities of the DPPH and hydroxyl radicals in a dose-dependent relationship. The highest scavenging rates of the DPPH and hydroxyl radicals were 40.03% and 92.97%, respectively, at an essential oil concentration of 10 mg/mL. The Artemisia annua essential oil significantly inhibited the growth of both Staphylococcus aureus and Escherichia coli, with inhibitory zones of 12.67±0.29 mm and 9.27±0.25 mm, respectively. The LD50 value of the Artemisia annua essential oil was 7491 mg/kg, indicating that it was not toxic. This study can provide a theoretical reference for the extraction and use of Artemisia annua and other Artemisia plants.

【Objective】The genetic transformation of pepper mediated by Agrobacterium was a very difficult process, and no efficient transformation system had been established so far.Green fluorescent protein (GFP) gene is a common reporter gene in plant genetic transformation.In the study, GFP was used as the reporter gene to optimize the Agrobacterium-mediated genetic transformation system of pepper.【Method】By using GFP expression system, three types of explants(cotyledons, hypocotyls and Flamingo-bill explants)from 3 pepper varieties('HP' '8214' and 'L55')were counted according to the adventitious bud differentiation rate, adventitious root differentiation rate and fluorescence positive rate.The effects of factors including infection concentration and infection time, pre-culture time and co-culture time on adventitious bud differentiation rate, adventitious root differentiation rate and fluorescence positive rate were explored.【Result】The adventitious bud differentiation rate of Flamingo-bill explants was significantly higher than that of the hypocotyl and cotyledon explants, among which the 'L55' Flamingo-bill explant had the highest adventitious bud differentiation rate of 77.59%.Therefore, the 'L55' Flamingo-bill explant was selected for subsequent research.Under 4 different combinations of Agrobacterium infection concentration and infection time, all of them could produce adventitious buds, adventitious roots and GFP-expressing calluses.When the infection concentration of Agrobacterium was OD600=0.05 and the infection time was 30 min, the adventitious bud differentiation rate and fluorescence positive rate of Flamingo-bill explants were the highest, reaching 48.39% and 4.84%, respectively.Under 6 different pre-culture and co-culture time combinations, the Flamingo-bill explants also produced adventitious buds and adventitious roots, and the highest adventitious bud differentiation rate and fluorescence positive rate were 48.44% and 12.50%, respectively, under the treatment of pre-culture for 1 d and co-culture for 1-2 d.Finally, PCR detection of adventitious roots and calluses with GFP fluorescence expression showed that the 3 target genes GFP, Kan and Cas9 all presented signal in the fluorescence positive tissues, indicating that the T-DNA insertion mediated by Agrobacterium was successful and the transformation was stable.【Conclusion】The explant type of pepper, Agrobacterium infection concentration, infection time, pre-culture time and co-culture time all have effects on the genetic transformation efficiency of pepper.Screening appropriate transformation conditions with GFP as a reporter gene could improve the efficiency of Agrobacterium-mediated genetic transformation of pepper.

Abstract Background Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. Results Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. Conclusions This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.

Abstract Freeze–thaw failure of frozen rock slope often occurs during engineering construction and mining in cold area, which poses a great threat to engineering construction and people's life safety. The properties of rock mass in cold region will change with the periodic change of temperature, which makes it difficult to accurately evaluate the stability of slope under the action of freeze–thaw cycle by conventional methods. Based on field investigation and literature review, this paper discusses the characteristics of frozen rock mass and the failure mechanism of frozen rock slope, and gives the types and failure modes of frozen rock slope. Then, the research status of frozen rock slope is analyzed. It is pointed out that the failure of frozen rock slope is the result of thermo-hydro-mechanical (THM) coupling. It is considered that freeze–thaw cycle, rainfall infiltration and fracture propagation have significant effects on the stability of frozen rock slope, and numerical simulation is used to demonstrate. The research shows that the safety factor of frozen rock slope changes dynamically with the surface temperature, and the safety factor of slope decreases year by year with the increase of freeze–thaw cycles, and the fracture expansion will significantly reduce the safety factor. Based on the above knowledge, a time-varying evaluation method of frozen rock slope stability based on THM coupling theory is proposed. This paper can deepen scholars' understanding of rock fracture slope in cold area and promote related research work.

Abstract To investigate the short-term effects and differences between exercise alone and exercise combined with self-mobilization training on chronic non-specific neck pain (CNSNP). Thirty subjects who met the criteria were recruited and randomly assigned to the exercise training group, the exercise combined with cervical self-mobilization training group (ECCM), and the exercise combined with cervicothoracic self-mobilization training group (ECCTM). The exercise training group received 6 weeks of deep neck flexor under biofeedback and scapular stability training, and the other two groups received 6 weeks of cervical self-mobilization and cervicothoracic self-mobilization, respectively, in addition to exercise training. Neck pain, cervical range of motion (ROM), neck disability, strength and endurance of deep neck flexor and quality of life were assessed before and after 6 weeks of training. The study results showed that all the three training programs for 6 weeks increased the strength and endurance of deep neck flexor, increased cervical ROM, reduced pain, and improved neck function (P

Repairing mechanical hole out of dimension tolerance of aluminum (Al) alloy has a high potential and function in manufacturing industries. To achieve a reliably repaired hole of 2024 Al alloy, radial-additive friction stir repairing (R-AFSR) was developed, and this technology was divided into the regularizing-defect and repairing stages. Results showed that by adjusting the filling depth of pinless tool at the regularizing-defect stage and the rotating direction of tool with threaded pin at the repairing stage, the sufficient metallurgical bonding was achieved and then the kissing bond defect was eliminated due to not only the enlarged stir zone but also the heightened pressure and temperature. Under the suitable processing parameters, the maximum tensile and compressive shear strengths of the repaired hole by R-AFSR were 281.8 and 206.8 MPa, which were 89.1 % and 95.1 % of those of the standard hole. The fracture mode of repaired hole was decided by the metallurgical bonding effect of interface between filling material (FM) and base material (BM) (the FM/BM interface), and three fracture modes, including tensile fracture, tensile-plug fracture and plug fracture, were obtained. The R-AFSR provides a new approach to acquiring a high-quality repaired mechanical hole of Al alloy.

Soil salinization seriously affects soil microbial diversity, and crop yield and quality worldwide. Microorganisms play a vital role in the process of crop yield and quality. Traditional Chinese medicine Glycyrrhiza uralensis Fisch. (licorice) can grow tenaciously in the heavily salinized land. However, the relationship between licorice plants and soil microorganisms is not clear. A field experiment was carried out to explore the effects of three different degrees of salinized soils on (i) licorice crop performance indicators, (ii) soil physical and chemical properties, and (iii) the changes in soil bacterial community structure and functional diversity in a semi-arid area of northwest China. The results showed that with the aggravation of soil salinization, the licorice yield, soil nutrients, and the bacterial abundance of Gemmatimonadetes and Myxococcota showed a downward trend, while the concentration of glycyrrhizic acid and liquiritin, and the bacterial abundance of Actinobacteria and Firmicutes showed an upward trend. The change of licorice yield mainly depended on the soil physical and chemical properties (e.g., EC and alkaline hydrolysable nitrogen). The change of licorice quality was more closely related to the change of bacterial diversity. The effect of bacterial diversity on liquiritin was greater than that on glycyrrhizic acid. Among them, Gemmatimonadetes were significantly negatively correlated with liquiritin and glycyrrhizic acid. These findings suggest that the increased soil Actinobacteria and Firmicutes or reduced Gemmatimonadetes and Myxococcota may provide a healthy and suitable living condition for the sustainable development of medicinal plant crops in a salinized soil ecosystem.

This study attempted to investigate relationship between rheumatoid arthritis and serum vitamin C levels using data from National Health and Nutrition Examination Survey (NHANES).The NHANES database aims to collect health, nutrition, biological, and behavioral data from a nationally representative sample of the population. This study utilizes NHANES data from three cycles: 2003–2004, 2005–2006, and 2017–2018, extracting data on the prevalence of rheumatoid arthritis and serum vitamin C levels. A generalized linear model is used to evaluate the association between the two.A total of 12,665 participants were included in the final analysis. Serum vitamin C levels were significantly higher in the non-rheumatoid arthritis group compared to the rheumatoid arthritis group (0.63 vs. 0.59, P = 0.042). Generalized linear model analysis showed that higher serum vitamin C levels were associated with a decreased risk of rheumatoid arthritis (OR = 0.62, 95 %CI: 0.40–0.98, P = 0.034). Stratified analysis revealed a significant interaction between non-hypertensive individuals and rheumatoid arthritis with serum vitamin C levels (P

Aim: Ovarian cancer (OC) is the most lethal gynecological malignancy, which seriously affects the prognosis and life quality of female patients. Therefore, new therapeutic targets and treatments are urgently needed. Methods: Expression levels of miR-93-5p and SLC7A11 and ferroptosis status in paracancerous and tumor tissues were examined and compared. The effect of the miR-93-5p-SLC7A11 regulatory loop on the malignant phenotype as well as the ferroptosis phenotype of SKOV3 cells was assessed. Furthermore, the interaction between miR-93-5p and SLC7A11 was confirmed via rescue experiment. Results: In this study, we found that miR-93-5p was lowly expressed in cancer tissues, and suggested that overexpression of miR-93-5p could target SLC7A11 to reduce its expression and promote ferroptosis, thereby inhibiting the malignant biological behaviors such as proliferation, invasion and migration, while knockdown of miR-93-5p restrained ferroptosis and promoting tumor growth. Besides, erastin, as a specific inhibitor of SLC7A11, could target down the expression of SLC7A11, induce the occurrence of ferroptosis, and reverse the effect of knockdown of miR-93-5p. Conclusions: Taken together, our findings disclosed that miR-93-5p increased the level of ferroptosis and inhibited the progression of OC by targeting and inhibiting the expression level of SLC7A11, which was a potential treatment in OC.

BackgroundEffective prevention is key to addressing the increasing prevalence and mortality of Alzheimer’s disease. Assessing the causal relationship between modifiable entertainment activity factors and the risk of Alzheimer’s disease is important for developing public health measures, but establishing causal relationships in epidemiological data may be challenging.MethodsThis study using the two-sample Mendelian randomization analysis aimed to investigate the causal effect of entertainment activity factors on the risk of Alzheimer’s disease. Summary statistics from publicly available genome-wide association studies were used to analyze 14 modifiable entertainment activity. The inverse variance weighted random effects method as the primary analytical method to estimate causal effects was used. Additionally performed MR-Egger, weighted median and weighted model methods to assess the robustness of the results. The reliability of our findings was validated through systematic sensitivity analyses and tests for heterogeneity.ResultsWe found significant correlation between time spent using computer (odds ratio 0.998; 95% confidence interval 0.996–0.999; p = 0.013) and Alzheimer’s disease, compared to other studied entertainment activities that had no significant causal relationship with Alzheimer’s disease.ConclusionOur findings support the hypothesis that increased computer use may reduce the risk of Alzheimer’s disease, providing potential strategic directions for the prevention of neurodegenerative diseases.

The development of modern information technology has led to significant demand for microoptical elements with complex surface profiles and nanoscale surface roughness. Therefore, various micro- and nanoprocessing techniques are used to fabricate microoptical elements and systems. Femtosecond laser direct writing (FsLDW) uses ultrafast pulses and the ultraintense instantaneous energy of a femtosecond laser for micro-nano fabrication. FsLDW exhibits various excellent properties, including nonlinear multiphoton absorption, high-precision processing beyond the diffraction limit, and the universality of processable materials, demonstrating its unique advantages and potential applications in three-dimensional (3D) micro-nano manufacturing. FsLDW has demonstrated its value in the fabrication of various microoptical systems. This study details three typical principles of FsLDW, several design considerations to improve processing performance, processable materials, imaging/nonimaging microoptical elements, and their stereoscopic systems. Finally, a summary and perspective on the future research directions for FsLDW-enabled microoptical elements and stereoscopic systems are provided.

Abstract Background Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase the risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to the therapy of a variety of diseases through inflammation inhibition, immune regulation, and tissue repair functions. However, the application and study of hUC-MSC exosomes in POI remain limited. Methods Here, we first constructed four rat animal models: the POI-C model (the “cyclophosphamide-induced” POI model via intraperitoneal injection), the POI-B model (the “busulfan-induced” POI model), the POI-U model (the “cyclophosphamide-induced” POI model under ultrasonic guidance), and MS model (the “maternal separation model”). Second, we compared the body weight, ovarian index, status, Rat Grimace Scale, complications, and mortality rate of different POI rat models. Finally, a transabdominal ultrasound-guided injection of hUC-MSC exosomes was performed, and its therapeuticy effects on the POI animal models were evaluated, including changes in hormone levels, oestrous cycles, ovarian apoptosis levels, and fertility. In addition, we performed RNA-seq to explore the possible mechanism of hUC-MSC exosomes function. Results Compared with the POI-C, POI-B, and MS animal models, the POI-U model showed less fluctuation in weight, a lower ovarian index, fewer complications, a lower mortality rate, and a higher model success rate. Second, we successfully identified hUC-MSCs and their exosomes, and performed ultrasound-guided intraovarian hUC-MSCs exosomes injection. Finally, we confirmed that the ultrasound-guided exosome injection (termed POI-e) effectively improved ovarian hormone levels, the oestrous cycle, ovarian function, and fertility. Mechanically, hUC-MSCs may play a therapeutic role by regulating ovarian immune and metabolic functions. Conclusions In our study, we innovatively constructed an ultrasound-guided ovarian drug injection method to construct POI-U animal models and hUC-MSC exosomes injection. And we confirmed the therapeutic efficacy of hUC-MSC exosomes on the POI-U animal models. Our study will offer a better choice for new animal models of POI in the future and provides certain guidance for the hUC-MSCs exosome therapy in POI patients. Graphical abstract The schema of construction of different animal models, extraction and identifying hUC-MSCs and exosomes, therapy of ultrasound-guided hUC-MSCs exosome injection. Note: POI: premature ovarian insufficiency; hUC-MSCs: Human umbilical cord mesenchymal stem cells; POI-C: POI-cyclophosphamide; POI-B: POI-cyclophosphamide + Busulfan; POI-U: POI-Ultrasonic guidance cyclophosphamide injection; MS: POI-Maternal separation. POI-e: ultrasound-guided hUC-MSCs exosome injection; AMH: Anti-müllerian hormone; LH: Luteinizing hormone; FSH: Follicle-stimulating hormone; DA: dopamine; T: Testosterone; PRL: prolactin; GnRH: Gonadotropin-releasing hormone.

Abstract Recent evidence suggests that allergic asthma (AA) decreases the risk of Coronavirus Disease 2019 (COVID-19). However, the reasons remain unclear. Here, we systematically explored data from GWAS (18 cohorts with 11,071,744 samples), bulk transcriptomes (3 cohorts with 601 samples), and single-cell transcriptomes (2 cohorts with 29 samples) to reveal the immune mechanisms that connect AA and COVID-19. Two-sample Mendelian randomization (MR) analysis identified a negative causal correlation from AA to COVID-19 hospitalization (OR = 0.968, 95% CI 0.940–0.997, P = 0.031). This correlation was bridged through white cell count. Furthermore, machine learning identified dendritic cells (DCs) as the most discriminative immunocytes in AA and COVID-19. Among five DC subtypes, only conventional dendritic cell 2 (cDC2) exhibited differential expression between AA/COVID-19 and controls (P

Abstract Background Evans and Hintermann lateral column lengthening (LCL) procedures are both widely used to correct adult acquired flatfoot deformity (AAFD), and have both shown good clinical results. The aim of this study was to compare these two procedures in terms of corrective ability and biomechanics influence on the Chopart and subtalar joints through finite element (FE) analysis. Methods Twelve patient-specific FE models were established and validated. The Hintermann osteotomy was performed between the medial and posterior facets of the subtalar joint; while, the Evans osteotomy was performed on the anterior neck of the calcaneus around 10 mm from the calcaneocuboid joint surface. In each procedure, a triangular wedge of varying size was inserted at the lateral edge. The two procedures were then compared based on the measured strains of superomedial calcaneonavicular ligaments and planter facia, the talus-first metatarsal angle, and the contact characteristics of talonavicular, calcaneocuboid and subtalar joints. Results The Hintermann procedure achieved a greater correction of the talus-first metatarsal angle than Evans when using grafts of the same size, indicating that Hintermann had stronger corrective ability. However, its distributions of von-Mises stress in the subtalar, talonavicular and calcaneocuboid joints were less homogeneous than those of Evans. In addition, the strains of superomedial calcaneonavicular ligaments and planter facia of Hintermann were also greater than those of Evans, but both generally within the safe range (less than 6%). Conclusion This FE analysis study indicates that both Evans and Hintermann procedures have good corrective ability for AAFD. Compared to Evans, Hintermann procedure can provide a stronger corrective effect while causing greater disturbance to the biomechanics of Chopart joints, which may be an important mechanism of arthritis. Nevertheless, it yields a better protection to the subtalar joint than Evans osteotomy. Clinical relevance Both Evans and Hintermann LCL surgeries have a considerable impact on adjacent joints and ligament tissues. Such effects alongside the overcorrection problem should be cautiously considered when choosing the specific surgical method. Level of evidence Level III, case–control study.

In the working process of the diaphragm slitting machine, a cascade control scheme based on the RBF network is proposed to address the tension fluctuation problem caused by the nonlinearity, strong coupling, and parameter variation of the unwinding system. Firstly, the dynamic characteristics of the unwinding process of the diaphragm slitting machine are analyzed, and the dynamic model of the unwinding section is established. The influencing factors causing tension fluctuation are studied. Then, a cascade control strategy combining sliding mode control (SMC) and RBF network adaptive sliding mode control (RBF-ASMC) is proposed to hierarchically control the key variables of unwinding tension and unwinding speed, which are coupled with each other. The sliding mode controller ensures stable control of the outer tension loop, and the RBF network adaptive sliding mode controller adds disturbance compensation and robust control to the inner speed loop. Finally, simulation and experimental results demonstrate that the cascade control scheme based on the RBF network weakens the coupling between key variables in the system, improves the dynamic performance, and enhances the disturbance rejection capability of the system.

Objective: It is a common clinical phenomenon that blood infiltrates into the injured tendon caused by sports injuries, accidental injuries, and surgery. However, the role of blood infiltration into the injured tendon has not been investigated. Methods: A blood-induced rat model was established and the impact of blood infiltration on inflammation and HO of the injured tendon was assessed. Cell adhesion, viability, apoptosis, and gene expression were measured to evaluate the effect of blood treatment on tendon stem/progenitor cells (TSPCs). Then RNA-seq was used to assess transcriptomic changes in tendons in a blood infiltration environment. At last, the small molecule drug PI3K inhibitor LY294002 was used for in vivo and in vitro HO treatment. Results: Blood caused acute inflammation in the short term and more severe HO in the long term. Then we found that blood treatment increased cell apoptosis and decreased cell adhesion and tenonic gene expression of TSPCs. Furthermore, blood treatment promoted osteochondrogenic differentiation of TSPCs. Next, we used RNA-seq to find that the PI3K/AKT signaling pathway was activated in blood-treated tendon tissues. By inhibiting PI3K with a small molecule drug LY294002, the expression of osteochondrogenic genes was markedly downregulated while the expression of tenonic genes was significantly upregulated. At last, we also found that LY294002 treatment significantly reduced the tendon HO in the rat blood-induced model. Conclusion: Our findings indicate that the upregulated PI3K/AKT signaling pathway is implicated in the aggravation of tendon HO. Therefore, inhibitors targeting the PI3K/AKT pathway would be a promising approach to treat blood-induced tendon HO.

Vaccination is widely acknowledged as an affordable and cost-effective approach to guard against infectious diseases. It is important to take vaccination rate, vaccine effectiveness, and vaccine-induced immune decline into account in epidemic dynamical modeling. In this paper, an epidemic dynamical model of vaccination is developed. This model provides a framework of the infectious disease transmission dynamics model through qualitative and quantitative analysis. The result shows that the system may have multiple equilibria. We used the next-generation operator approach to calculate the maximum spectral radius, that is, basic reproduction number $ {R_{vac}} $. Next, by dividing the model into infected and uninfected subjects, we can prove that the disease-free equilibrium is globally asymptotically stable when $ {R_{vac}} < 1 $, provided certain assumptions are satisfied. When $ {R_{vac}} > 1 $, there exists a unique endemic equilibrium. Using geometric methods, we calculate the second compound matrix and demonstrate the Lozinskii measure $ \bar q \leqslant 0 $, which is equivalent to the unique endemic equilibrium, which is globally asymptotically stable. Then, using center manifold theory, we justify the existence of forward bifurcation. As the vaccination rate decreases, the likelihood of forward bifurcation increases. We also theoretically show the presence of Hopf bifurcation. Then, we performed sensitivity analysis and found that increasing the vaccine effectiveness rate can curb the propagation of disease effectively. To examine the influence of vaccination on disease control, we chose the vaccination rate as the optimal vaccination control parameter, using the Pontryagin maximum principle, and we found that increasing vaccination rates reduces the number of infected individuals. Finally, we ran a numerical simulation to finalize the theoretical results.

Objective This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. Methods Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. Results Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway. Conclusion Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.

Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient. In this study, a one-tube dual recombinase polymerase amplification (RPA) reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay, named ''Dual-RPA-LFD'', to visualize the dual detection of genetically modified (GM) crops. In which, the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits. Gradient diluted plasmids, transgenic standards, and actual samples were used as templates to conduct sensitivity, specificity, and practicality assays, respectively. The constructed method achieved the visual detection of plasmid at levels as low as 100 copies, demonstrating its high sensitivity. In addition, good applicability to transgenic samples was observed, with no cross-interference between two test lines and no influence from other genes. In conclusion, this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37 ℃ in a rapid, equipment-free field manner, providing a new alternative for rapid screening for transgenic assays in the field.

Given the escalating severity of colitis caused by Salmonella infection and the growing challenge of drug resistance, there is an urgent demand for novel and effective treatment strategies with minimal side effects. Herein, we explored the potential therapeutic effects of polysaccharides on Ulcerative Colitis (UC). Our results showed that both purified polysaccharide from Dendrobium devonianum (DVP-1) and Crude polysaccharides from Dendrobium devonianum (CP) pre-treatment could prevent colon shortening and spleen enlargement, and alleviate colonic tissue damage. Western blot and RT-qPCR analyses revealed that DVP-1 and CP downregulated pro-inflammatory mediators while upregulating the expression of the anti-inflammatory mediator and tight junction proteins. Besides, 16S rRNA sequencing analysis showed that DVP-1 modulated gut dysbiosis by increasing the relative abundance of ClostridiumXlVa, and reducing the relative abundance of Alloprevotella. Additionally, DVP-1 and CP significantly increased the concentrations of tryptophan metabolites while decreasing purine metabolites. Taken together, these findings suggest that DVP-1 and CP yield potential benefits in alleviating UC primarily through restoring intestinal barrier function and regulating intestinal microbiota.

In this report, we present an Asian male patient who was 30 years old and admitted to the hospital due to pancreatitis. While undergoing a CT scan, an isolated mass was unexpectedly discovered in the patient’s abdomen. The patient’s abdominal pain, which was caused by pancreatitis, had resolved before he underwent surgical resection to remove the mass. Subsequently, the patient was diagnosed with Castleman disease based on pathology. Castleman disease occurring in the mesentery is exceptionally rare. Therefore, we have reviewed the essential information regarding Castleman disease and have found that the crucial part lies in the diagnosis and the consideration of distinct treatment strategies based on different types.

Licorice is a well-known Chinese medicinal plant that is widely used to treat multiple diseases and process food; however, wild licorice is now facing depletion. Therefore, there is an urgent need to identify and protect licorice germplasm diversity. In this study, metabolomic and transcriptomic analyses were conducted to investigate the biodiversity and potential medicinal value of the rare wild Glycyrrhiza squamulose. A total of 182 differentially accumulated metabolites and 395 differentially expressed genes were identified by comparing Glycyrrhiza uralensis and Glycyrrhiza squamulose. The molecular weights of the chemical component of G. squamulose were comparable with those of G. uralensis, suggesting that G. squamulose may have medicinal value. Differentially accumulated metabolites (DAMs), mainly flavonoids such as kaempferol-3-O-galactoside, kaempferol-3-O-(6ʺmalonyl) glucoside, and hispidulin-7-O-glucoside, showed potential vitality in G. squamulose. Comparative transcriptomics with G. uralensis showed that among the 395 differentially expressed genes (DEGs), 69 were enriched in the isoflavonoid biosynthesis pathway. Multiomics analysis showed that the distinction in flavonoid biosynthesis between G. squamulose and G. uralensis was strongly associated with the expression levels of IF7GT and CYP93C. In addition to identifying similarities and differences between G. squamulose and G. uralensis, this study provides a theoretical basis to protect and investigate rare species such as G. squamulose.

[Abstract]: Objective: This study aimed to investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) and any possible interactions between specific MTHFR alleles and traditional risk factors among a Han Chinese cohort. Methods: 434 AIS patients were consecutively recruited between January 2017 and June 2019, including 129 END and 305 non-END cases. A candidate gene association study design was used to analyze the association between MTHFR gene polymorphism and END risk. The polymerase chain reaction-restriction fragment length polymorphism (RFLP) method was employed to genotype the MTHFR C677T polymorphism. The interactional analyses were performed using the multifactor dimensionality reduction test. Results: Hyperglycemia (odds ratio [OR]: 2.410, 95 % confidence interval [CI]: 1.436–4.046, p = 0.001), neurological function impairment (NIHSS score >5) (OR: 2.158, 95%CI: 1.337–3.484, p = 0.002) on admission, and hyperhomocysteinemia (HHcy) (OR: 2.570, 95%CI: 1.229–5.376, p = 0.012) were independently associated with END. The TT genotype (OR: 1.710, 95%CI: 1.021–2.863, p = 0.043) and T allele (OR: 1.710, 95%CI: 1.021–2.863, p = 0.043) of this C677T polymorphism were associated with susceptibility to END, and the TT genotype was more common in the subjects with HHcy (OR: 2.525, 95%CI: 1.111–5.739, P = 0.023). In addition, we also found interactions for END risk between the C677T polymorphism and traditional risk factors for END, including: hyperglycemia on admission, drinking, and moderate to severe neurological deficits (OR 1.237, 95 % CI 0.227–6.734), although the results were not statistically significant (p = 0.806). Conclusions: Our results show a possible association between MTHFR C677T polymorphism and gene–environment interactions with END susceptibility in a Han Chinese cohort.

The interaction of rotating machine elements with fluid in gearboxes results in fluid flow and no-load power loss. A targeted design of the gearbox lubrication system enables a reliable operation under economical and sustainable use of lubricant. This study focuses on the influence of various parameters on the oil flow and no-load gear power loss of a dip-lubricated single-stage gearbox. Numerical, experimental, and analytical results are presented and compared. A single numerical simulation setup without parameter-specific tuning is applied for a wide range of parameters. The evaluated wetted gear surface strongly depends on the circumferential speed and shows a strong correlation with the resulting no-load gear loss torque. At lower circumferential speed, the wetted gear surface decreases before increasing at higher circumferential speed. Numerical and experimental results show good agreement in terms of magnitude and trend. The analytical approaches underestimate the numerical and experimental results. Nevertheless, they do provide a good representation of the trends in terms of the influence of immersion depth and rotation direction.

BackgroundBased on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed.MethodsThis multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS).ResultsForty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%).ConclusionAnlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.

Abstract Breast cancer classification and segmentation play an important role in identifying and detecting benign and malignant breast lesions. However, segmentation and classification still face many challenges: 1) The characteristics of cancer itself, such as fuzzy edges, complex backgrounds, and significant changes in size, shape, and intensity distribution make accurate segment and classification challenges. 2) Existing methods ignore the potential relationship between classification and segmentation tasks, due to the classification and segmentation being treated as two separate tasks. To overcome these challenges, in this paper, a novel Semantic‐aware transformer (SaTransformer) for breast cancer classification and segmentation is proposed. Specifically, the SaTransformer enables doing the two takes simultaneously through one unified framework. Unlike existing well‐known methods, the segmentation and classification information are semantically interactive, reinforcing each other during feature representation learning and improving the ability of feature representation learning while consuming less memory and computational complexity. The SaTransformer is validated on two publicly available breast cancer datasets – BUSI and UDIAT. Experimental results and quantitative evaluations (accuracy: 97.97%, precision: 98.20%, DSC: 86.34%) demonstrate that the SaTransformer outperforms other state‐of‐the‐art methods.

To explore the development of coal seam fractures around gas extraction borehole and the issue of self-ignition caused by air leakage, a combination of theoretical analysis, field testing, and laboratory experiments was used. The distribution characteristics of cracks in the crushed zone after borehole excavation were analyzed. An in-situ test using SF6 tracer gas was conducted to measure air leakage in the gas extraction borehole, revealing the law of air leakage around the gas extraction borehole during the process of gas pre-extraction. Using a program for temperature increase and gas chromatography combined experiment, the self-ignition characteristic parameters of coal under different air supply rates were studied as a research object of the 215 working face in a certain mine, and the functional relationship formula between oxygen consumption rate, CO generation rate, and coal temperature and air supply rate was obtained. The results showed that the main ways of air leakage around the gas extraction borehole were side leakage of roadway coal wall, drilling fracture leakage, and sealing section leakage. The minimum air leakage rate around the gas extraction borehole was quantitatively obtained between 0.19 m/min and 0.68 m/min, with an average air leakage rate of 0.41 m/min, and the range of air leakage in the borehole was greater than 4.35 m. The air supply rate had a promoting effect on the natural characteristics parameters of coal.

Abstract As current trend for physician tools, ChatGPT can sift through massive amounts of information and solve problems through easy-to-understand conversations, ultimately improving efficiency. Mycosis is currently facing great challenges, including high fungal burdens, high mortality, limited choice of antifungal drugs and increasing drug resistance. To address these challenges, We asked ChatGPT for fungal infection scenario-based questions and assessed its appropriateness, consistency, and potential pitfalls. We concluded ChatGPT can provide compelling responses to most prompts, including diagnosis, recommendations for examination, treatment and rational drug use. Moreover, we summarized exciting future applications in mycosis, such as clinical work, scientific research, education and healthcare. However, the largest barriers to implementation are deficits in indiviudal advice, timely literature updates, consistency, accuracy and data safety. To fully embrace the opportunity, we need to address these barriers and manage the risks. We expect that ChatGPT will become a new weapon in in the battlefield of mycosis.

Abstract Background Peanut is an important oil crop worldwide. Peanut web blotch is a fungal disease that often occurs at the same time as other leaf spot diseases, resulting in substantial leaf drop, which seriously affects the peanut yield and quality. However, the molecular mechanism underlying peanut resistance to web blotch is unknown. Results The cytological examination revealed no differences in the conidium germination rate between the web blotch-resistant variety ZH and the web blotch-susceptible variety PI at 12–48 hpi. The appressorium formation rate was significantly higher for PI than for ZH at 24 hpi. The papilla formation rate at 36 hpi and the hypersensitive response rate at 60 and 84 hpi were significantly higher for ZH than for PI. We also compared the transcriptional profiles of web blotch-infected ZH and PI plants at 0, 12, 24, 36, 48, 60, and 84 hpi using an RNA-seq technique. There were more differentially expressed genes (DEGs) in ZH and PI at 12, 36, 60, and 84 hpi than at 24 and 48 hpi. Moreover, there were more DEGs in PI than in ZH at each time-point. The analysis of metabolic pathways indicated that pantothenate and CoA biosynthesis; monobactam biosynthesis; cutin, suberine and wax biosynthesis; and ether lipid metabolism are specific to the active defense of ZH against YY187, whereas porphyrin metabolism as well as taurine and hypotaurine metabolism are pathways specifically involved in the passive defense of ZH against YY187. In the protein-protein interaction (PPI) network, most of the interacting proteins were serine acetyltransferases and cysteine synthases, which are involved in the cysteine synthesis pathway. The qRT-PCR data confirmed the reliability of the transcriptome analysis. Conclusion On the basis of the PPI network for the significantly enriched genes in the pathways which were specifically enriched at different time points in ZH, we hypothesize that serine acetyltransferases and cysteine synthases are crucial for the cysteine-related resistance of peanut to web blotch. The study results provide reference material for future research on the mechanism mediating peanut web blotch resistance.

In order to avoid the depth increasing of repaired hole and eliminate the super-fine grain band in stir zone by radial-additive friction stir repairing (R-AFSR), a solid-state repairing technique of active-passive radial-additive friction stir repairing (AP-RAFSR) assisted by the truncated cone-shaped filling material was proposed in this study. The mechanical hole out of dimension tolerance of AZ31 magnesium alloy was chosen as the repaired object. The results indicated that the AP-RAFSR process rather than the R-AFSR process avoided the kissing bond in the bottom of the repairing interface under the condition of the tool pin length equal to the height of the standard mechanical hole. The continuously-distributed and large-length super-fine grain bands were eliminated in the stir zone by AP-RAFSR. The maximum tensile and compressive-shear strengths of repaired hole by AP-RAFSR reached 190.6 MPa and 138.9 MPa at 1200 rpm respectively, which were equivalent to 97.7% and 89.6% of those of the standard mechanical hole. This AP-RAFSR process assisted by the truncated cone-shaped filling material provides a new technique to obtain a no-depth-increasing, defect-free and high-strength repaired mechanical hole.

Nowadays, living therapeutics is a promising candidate among various therapies, and oral administration of living therapeutics characterized by universality and safety avail to make the transition from bench to bedside. However, precise delivery and continuous maintenance of cell viability and activity to acquire stable and ideal therapeutic efficacy remain challenging. Living material is the smart integration of the flexibly programmable functionality of biomaterial and the autonomous environmental responsiveness of living elements, heralding a new era of biotherapeutics in addressing human health concerns. Here, our review aims at presenting an overview of the status of the oral delivery of living material from a biological, technical, and practical perspective, describing the clinical significance and potential, the current technological development and dilemma, as well as the prospect.

To overcome the difficulty of vascular regeneration in exposed tendon wounds, we combined human placenta-derived mesenchymal stem cells (hPMSCs) with an artificial dermal scaffold and assessed their role in promoting vascular regeneration and wound healing in vivo . hPMSCs were isolated from the human placenta and characterized based on their morphology, phenotypic profiles, and pluripotency. New Zealand rabbits were used to establish an exposed tendon wound model, and hPMSCs and artificial dermal scaffolds were transplanted into the wounds. The results of gross wound observations and pathological sections showed that hPMSCs combined with artificial dermal scaffold transplantation increased the vascularization area of the wound, promoted wound healing, and increased the survival rate of autologous skin transplantation. Following artificial dermal scaffold transplantation, hPMSCs accelerated the vascularization of the dermal scaffold, and the number of fibroblasts, collagen fibers, and neovascularization in the dermal scaffold after 1 week were much higher than those in the control group. Immunohistochemical staining further confirmed that the expression of the vascular endothelial cell marker, CD31, was significantly higher in the combined transplantation group than in the dermal scaffold transplantation group. Our findings demonstrated that hPMSCs seeded onto artificial dermal scaffold could facilitate vascularization of the dermal scaffold and improve tendon-exposed wound healing.

Introduction The worldwide prevalence of myopia is high and continues to increase. In this study, a school screening programme for myopia will be implemented using the whole-process information method. The purpose of this study is to investigate the prevalence of myopia in urban and rural areas of Northeast China and to determine the factors related to myopia.Methods and analysis This is a school-based cross-sectional study. Our study population will include 6000 school-aged children from 2 urban and 2 rural schools in Jinzhou, China. The study will be conducted using our self-developed internet-based intelligent data collection, transmission, storage and analysis system. Examination parameters include uncorrected distance visual acuity, presenting distance visual acuity, non-cycloplegic autorefraction, height, weight, waist circumference, hip circumference, spinal curvature and dental caries. The examination report will be automatically sent to parents, who will complete the questionnaire, and appropriate statistical analysis will be performed. The main outcome is the prevalence of myopia, defined as an equivalent spherical degree ≤−0.5 D.Ethics and dissemination Ethical approval was obtained from the Third Affiliated Hospital of Jinzhou Medical University (number: JYDSY-KXYJ-IEC-2023-018). Findings will be published in a peer-reviewed journal. Subjects and their parents (or other authorised agents) give informed consent prior to study participation.Trial registration number ChiCTR2300072893.

ObjectiveTo investigate the relationship between serum uric acid (SUA) levels and ischemic stroke in young patients in the Ganzi Tibetan plateau area.MethodsA cross-sectional survey was undertaken from January 2020 to June 2023 involving young patients (age: 15–45 years) diagnosed with ischemic stroke. The survey was conducted at the Department of Internal Medicine of the People’s Hospital of Derong County, Ganzi Prefecture. The participants underwent a comprehensive assessment, including questionnaire surveys, physical examinations, laboratory tests, and head computed tomography (CT) examinations. Based on the tertiles of serum uric acid (SUA) levels, the patients were stratified into three groups. Furthermore, stroke severity was classified into mild (1–4 points), moderate (5–15 points), and severe (>15 points) categories using the National Institute of Health Stroke Scale.ResultsThe severe stroke group exhibited higher levels of age, glucose, systolic blood pressure, serum triglyceride, low-density lipoprotein cholesterol, and serum uric acid (SUA) compared to the mild stroke group (P < 0.05). Furthermore, the likelihood of male sex, advanced age, smoking, and a family history of stroke, diabetes mellitus, and heart disease were significantly elevated in the severe stroke group compared to the moderate stroke group (P < 0.05). Multivariate logistic regression analysis conducted on young adults residing in highland areas revealed a significant association between SUA levels and the risk of stroke.ConclusionElevated SUA levels serve as a distinct risk factor for the development of a major stroke in young patients in highland areas. At SUA levels of 320.56 mol/L, the risk of a moderate-to-severe stroke is noticeably elevated.

Pressure buildup testing can be used to analyze fracture network characteristics and conduct quantitative interpretation of relevant parameters for shale gas wells, thus providing bases for assessing the well productivity and formulating proper development strategies. This study establishes a new well test interpretation model for fractured horizontal wells based on seepage mechanisms of shale reservoirs and proposes a method for identifying fracturing patterns based on the characteristic slopes of pressure buildup curves and curve combination patterns. The pressure buildup curve patterns are identified to represent three types of shale reservoirs in the Sichuan Basin, namely the moderately deep shale reservoirs with high pressure, deep shale reservoirs with ultra-high pressure, and moderately deep shale reservoirs with normal pressure. Based on this, the relationship between the typical pressure buildup curve patterns and the fracture network types are put forward. Fracturing effects of three types of shale gas reservoir are compared and analyzed. The results show that typical flow patterns of shale reservoirs include bilinear flow in primary and secondary fractures, linear flow in secondary fractures, bilinear flow in secondary fractures and matrix, and linear flow in matrix. The fracture network characteristics can be determined using the characteristic slopes of pressure buildup curves and curve combinations. The linear flow in early secondary fractures is increasingly distinct with an increase in primary fracture conductivity. Moreover, the bilinear flow in secondary fractures and matrix and the subsequent linear flow in the matrix occur as the propping and density of secondary fractures increase. The increase in the burial depth, in-situ stress, and stress difference corresponds to a decrease in the propping of primary fractures that expand along different directions in the shale gas wells in the Sichuan Basin. Four pressure buildup curve patterns exist in the Sichuan Basin and its periphery. The pattern of pressure buildup curves of shale reservoirs in the Yongchuan area can be described as 1/2 → 1/4, indicating limited stimulated reservoir volume, poorly propped secondary fractures, and the forming of primary fractures that extend only to certain directions. The pressure buildup curves of shale reservoirs in the main block of the Fuling area show a pattern of 1/4 → 1/2 or 1/2, indicating greater stimulated reservoir volume, well propped secondary fractures, and the forming of complex fracture networks. The pattern of pressure buildup curves of shale reservoirs in the Pingqiao area is 1/2 → 1/4 → 1/2, indicating a fracturing effect somewhere between that of the Fuling and Yongchuan areas. For reservoirs with normal pressure, it is difficult to determine fracture network characteristics from pressure buildup curves due to insufficient formation energy and limited liquid drainage.

This study sought to explore the effects and potential mechanisms of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata to alleviate lipopolysaccharide (LPS)-induced intestinal epithelium injury in broilers. A total of 486 1-day-old broilers were assigned at random to a control (CON) group, LPS group, and LPS+IA group in a 21-d study. The CON and LPS groups received a basal diet, while the LPS+IA group received a basal diet supplemented with 0.6 mg/kg IA. At 17, 19, and 21 days of age, the LPS and LPS+BP groups were injected intraperitoneally with LPS, and the CON group was intraperitoneally injected equivalent amount of saline solution. The results manifested that LPS injection caused intestinal inflammation and lipid peroxidation, disrupted intestinal barrier and function, and increased the abundance of harmful microorganisms. However, dietary IA supplementation alleviated LPS-induced adverse changes in intestinal morphology, apoptosis, mucosal barrier integrity, cecum microorganisms, and homeostasis disorder by decreasing inflammatory cytokines and enhancing antioxidant-related genes expressions; inhibited LPS-induced increases in TLR4 and NF-κB expressions and decreases in Nrf2 and GPX1 genes expressions. Our findings indicated that Macleaya cordata IA addition attenuated LPS-induced intestinal epithelium injury and disorder of intestinal homeostasis by enhancing the anti-inflammatory and antioxidant capacity of broiler chickens possibly via co-regulating TLR4/MyD88/NF-κB and Nrf2 signaling pathways.

ABSTRACT Microalgae are a potential source of biodiesel owing to their simple structure and high biomass and lipid production rates. Here, we demonstrate that fatty acid (FA) contents can be altered in Chlorella sp. JB6 in the presence of sodium bicarbonate (NaHCO3). We cloned the key genes necessary for FA de novo synthesis conserved in JB6, including biotin carboxyl carrier protein (BCCP), β-carboxyltransferase (β-CT), malonyl CoA-ACP malonyl transferase (MCMT), 3-ketoacyl-ACP reductase (KAR), β-ketoacyl-[acyl carrier protein] synthase I (KASI), and KASII, and successfully transferred plasmids carrying these genes into JB6 cells. We found that overexpression of BCCP, MCMT, KASI, and KASII inhibited the growth of JB6 cells and decreased their resistance to NaHCO3. Notably, ectopic expression of these genes promoted very long-chain saturated FA (>20 C) accumulation. Taken together, we demonstrate that these genes are critical for JB6 growth and resistance to NaHCO3 and can be used for metabolic engineering. IMPORTANCE Fatty acid (FA) contents can be altered in Chlorella JB6 in the presence of sodium bicarbonate (NaHCO3). Overexpression of the FA de novo synthesis genes inhibited the growth of JB6 cells and decreased their resistance to NaHCO3, but these transgenic JB6 strains could grow in a medium containing as high as 300 mM NaHCO3. In JB6, ectopic expression of the FA de novo synthesis genes increased the synthesis of very long-chain saturated FA (> 20C).

Background and purposeOff-clamp robot-assisted partial nephrectomy (Offc-RAPN) is a technically challenging procedure that can effectively avoid renal ischemia owing to the absence of hilar vessel preparation and clamping. However, data on the learning curve (LC) for this technique are limited. The purpose of this study was to assess the LC of Offc-RAPN and compare the perioperative outcomes between different learning phases.MethodsThis retrospective study included 50 consecutive patients who underwent purely Offc-RAPN between January 2022 and April 2023. Multidimensional cumulative sum (CUSUM) analysis method was used to assess LC. Spearman's correlation and LOWESS analysis were performed to analyze the continuous variables of perioperative outcomes. Baseline characteristics and perioperative outcomes were compared using χ2-test, t-test and U-test.ResultsCUSUM analysis identified two LC phases: phase I (the first 24 cases) and phase II (the subsequent 26 cases). Phase II showed significant reductions in mean operative time (133.5 vs. 115.31 min; p = 0.04), mean console time (103.21 vs. 81.27 min; p = 0.01), and mean postoperative length of stay (5.33 vs. 4.30 days; p = 0.04) compared to phase I. However, no significant differences were observed in other perioperative outcomes or baseline characteristics between the two LC phases.ConclusionsOffc-RAPN performed by a surgeon with experience in laparoscopic and robotic surgeries achieved early proficiency in 24 cases. Moreover, Offc-RAPN alone is safe and feasible even in the initial phase of the LC for an experienced surgeon.

ABSTRACT Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. Persistent human papillomavirus (HPV) infection is the principal cause of cervical cancer, with HPV16 and HPV18 accounting for about 70% of cases worldwide. Cervical screening is an effective secondary measure for preventing cervical cancer. Testing for HPV DNA is becoming increasingly important in cervical cancer screening. The existing PCR-based HPV detection technology has several disadvantages: the assays are time-consuming, and sophisticated equipment is required to control the temperature cycles. These drawbacks have led to the development of detection technologies based on isothermal amplification. Here, we present real-time recombinase polymerase amplification (RPA-exo)-based assays for single genotyping of either the E7 or the L1 segment of HPV16 or HPV18. These assays were highly sensitive, able to detect HPV in all clinical samples with Ct values below 34, and yielded results within 25 min. A dual-detection system capable of detecting both HPV16 and HPV18 in a single reaction was also developed based on the L1 gene. It has a limit of detection of approximately 10,000 copies of each genotype per reaction. The assays were validated with DNA extracted from 36 biopsy specimens and 42 exfoliated cell samples from 43 patients with cervical lesions at different stages. The RPA-exo system is a promising clinical detection platform with the advantages of yielding results rapidly and operating at a constant temperature, while being cost-effective and easy to use. IMPORTANCE HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.