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Although high temperatures influence gut health, data on underlying mechanisms remains scant. Using a pig model, this study performed a global analysis on how chronic heat stress affects the transport and immune function of the gut through transcriptome, proteome, microbial diversity and flow cytometry. A total of 27 pigs with similar body weights were assigned into 3 groups, control (Con) group (23 °C), chronic heat stressed (HS) group (33 °C), and pair-fed (PF) group, in a controlled environment for 21 days. Our results showed that pigs in the HS group had reduced growth performance and diminished height of ileal villi (P < 0.01). Transcriptome and proteome analyses demonstrated notable modification of expression of nutrients and ion transport-related transporters and gut mechanical barrier-related genes by chronic heart stress (P < 0.05), suggesting damage of transport functions and the gut barrier. Chronic heat stress-induced endoplasmic reticulum stress also increased the synthesis of misfolded proteins, leading to upregulation of misfolded protein degradation and synthesis, as well as vesicle transport disorder (P < 0.05). Energy supply processes were enhanced in the mitochondrion (P < 0.05) to maintain biological processes with high energy demands. Furthermore, chronic heat stress activated complement cascade response-related genes and proteins in the gut mucosa (P < 0.05). Our flow cytometry assays showed that the proportion of gut lymphocytes (CD4+ T cells, T cells, B cells in Peyer's patch lymphocytes and CD4+ CD25+ T cells in intraepithelial lymphocytes) were significantly altered in the HS group pigs (P < 0.05). In addition, the occurrence of gut microbial dysbiosis in the HS group pigs was characterized by increased potential pathogens (e.g., Asteroleplasma, Shuttleworthia, Mycoplasma) and suppression of beneficial bacteria (e.g., Coprococcus and Aeriscardovia), which are associated with gut immune function. Altogether, our data demonstrated that chronic heat stress induced gut transport and immune function disorder associated with endoplasmic reticulum stress in growing pigs.

A draft genome assembly of Cremastra appendiculata (D. Don) Makino, a traditional Chinese medicine plant, identified genes responsible for plant colchicine biosynthesis.

As online health communities (OHCs) continue to proliferate, narrative reviews on doctors have become a vital reference source for patients when choosing online health services. However, the potential value of subjective information reflecting patient experiences in OHCs has not been fully explored. The present study seeks to investigate the impact of narrative reviews on patients’ selection of e-doctors and the extent to which such reviews are moderated by doctors’ specialties. This paper collected data from 747 doctors and 105 032 reviews from WeDoctor, one of China’s most popular OHCs, in 2019. We employed Latent Dirichlet Allocation topic modeling to extract 3 topics and analyzed their effects on patient e-doctor choice using a multiple regression method. Our findings indicate that Topic 1, clinical skills and effects, had a positive impact on patient choice in OHCs ( β 1 = .243, P

Abstract Form drag of the blunt object occurs from the pressure difference due to the physical dimensions of the object obstructing and altering the flow of the fluid. The innovative approach of form drag reduction is realized by changing the shape of the blunt object to a streamlined body by introducing a cavity. The construction of superhydrophobic interfaces is widely considered as the best solution for introducing a cavity, because water is prevented from penetrating the space between the nanoscale structures, leading to a Cassie–Baxter wetting regime and then water splashing outward. Here, by introducing Janus nanostructure coating on hydrophobic spheres, it is found that the position (impacting direction) and coverage ratio (r) of the nanostructures, accurately manipulate the performance of water film on the sphere surface. When the nanostructure faces upward, the detached thin film develops to a splash crown only if r increases to 1/3 or even above. Correspondingly, the remaining open aperture aids in increasing the subsequent air entrainment, and an air‐entrainment cavity is trapped on the sphere surface. However, if the nanostructure faces downward, only a tiny region of the nanostructures (r ≤ 1/8) can help a thin liquid film directly develop into a splash crown and cavity.

Objectives This study aimed to screen the potential risk factors for academic burnout among adolescents during the COVID-19 pandemic, develop and validate a predictive tool based on the risk factors for predicting academic burnout.Design This article presents a cross-sectional study.Setting This study surveyed two high schools in Anhui Province, China.Participants A total of 1472 adolescents were enrolled in this study.Outcome measures The questionnaires included demographic characteristic variables, living and learning states and adolescents’ academic burnout scale. Least absolute shrinkage and selection operator and multivariate logistic regression analyses were employed to screen the risk factors for academic burnout and develop a predictive model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to assess the accuracy and discrimination of the nomogram.Results In this study, 21.70% of adolescents reported academic burnout. Multivariable logistic regression analysis showed that single-child family (OR=1.742, 95% CI: 1.243 to 2.441, p=0.001), domestic violence (OR=1.694, 95% CI: 1.159 to 2.476, p=0.007), online entertainment (>8 hours/day, OR=3.058, 95% CI: 1.634 to 5.720, p

Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), β-tricalcium phosphate (β-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.

Heterostructured materials show great potential to enhance the specific capacity, rate performance and cycling lifespan of lithium-ion batteries owing to their unique interfaces, robust architectures, and synergistic effects. Herein, a polypyrrole (PPy)-coated nanotube-like Mo3S4/CoMo2S4 heterostructure is prepared by the hydrothermal and subsequent in situ polymerization methods. The well-designed nanotube-like structure is beneficial to relieve the serious volume changes and facilitate the infiltration of electrolytes during the charge/discharge process. The Mo3S4/CoMo2S4 heterostructure could effectively enhance the electrical conductivity and Li+ transport kinetics owing to the refined energy band structure and the internal electric field at the heterostructure interface. Moreover, the conductive PPy-coated layer could inhibit the obvious volume expansion like a firm armor and further avoid the pulverization of the active material and aggregation of generated products. Benefiting from the synergistic effects of the well-designed heterostructure and PPy-coated nanotube-like architecture, the prepared Mo3S4/CoMo2S4 heterostructure delivers high reversible capacity (1251.3 mAh g−1 at 300 mA g−1), superior rate performance (340.3 mAh g−1 at 5.0 A g−1) and excellent cycling lifespan (744.1 mAh g−1 after 600 cycles at a current density of 2.0 A g−1). Such a design concept provides a promising strategy towards heterostructure materials to enhance their lithium storage performances and boost their practical applications.

Litsea cubeba is a characteristic woody oil resource in Hunan. As a solid waste of woody oil resources, Litsea cubeba kernels are rich in Litsea cubeba kernel oil with a carbon chain length of C10–12 fatty acid. In this work, aliphatic hydroxamic acids (AHAs) with carbon chain lengths of C10–12 were prepared from Litsea cubeba kernel oil via methylation and hydroximation reactions. The adsorption and hydrophobicity mechanism of AHA towards wolframite was explored by contact angle, zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The flotation results demonstrated that AHA was a superior collector than the traditional collector such as benzoyl hydroxamic acid (BHA). Zeta potential and contact angle results have shown that AHA was adsorbed on the surface of the Fe(III)-activated wolframite in its anionic form, which significantly improved the surface hydrophobicity of wolframite. FTIR and XPS revealed that AHA was chemically adsorbed on the surface of Fe(III)-activated wolframite in the form of a five-member ring, which made the hydrophobic chain reach into the solution, come in contact with bubbles, and achieve flotation separation.

Phytase activity can be impaired during pelleting because of extreme thermal conditions. This study investigated the effects of dose and source of phytase on phytase activity during the conditioning, pelleting, and cooling process. A split-plot design was used in two experiments, with five phytase doses (Exp. 1; 7560, 14310, 33830, 43590 and 61500 FTU/kg) or eight phytase sources (Exp. 2) as the main plot and steam conditioning temperatures (Exp. 1 and 2; 75 and 85 °C) as the subplot. Each treatment processed four batches, one batch per replicate. The results of Exp. 1 showed phytase dose in diets had no effect (p > 0.05) on the recovery rate of phytase activity after the conditioning, pelleting, or cooling process. The recovery rate of phytase activity in each process was higher (p < 0.05) at 75 °C than that at 85 °C for both Exp. 1 and 2. The phytase source significantly affected (p < 0.05) the recovery rate of phytase activity and had varied appearances of structure. In conclusion, the structure, phytase activity, and phytase recovery after steam conditioning–pelleting significantly varied across sources, but the stability of phytase was not affected by dose.

To obtain good productive performance, sows have different nutrition requirements at different gestation periods. However, in gestation stalls, conventional feeders have large relative errors, management is difficult because of the large numbers of sows, and there are shortcomings in feeding precision and data management. In order to achieve precision feeding and enhance the control of multiple feeders for gestating sows housed in stalls, this study was carried out to investigate a precision feeding system that could be controlled at multiple levels. This system consisted of an electronic sow feeder (ESF), controller area network (CAN), personal digital assistant (PDA), central controller, and Internet of Things platform (IoTP). The results of the experiment showed that relative errors of 60 ESFs delivering feed were within ±2.94%, and the coefficient of variation was less than 1.84%. When the received signal strength indicator (RSSI) ranged from −80 dbm to −70 dbm, the packet loss rate of the PDA was 3.425%. When the RSSI was greater than −70 dbm, no packet loss was observed, and the average response time was 556.05 ms. The IoTP was at the performance bottleneck when the number of concurrent threads was greater than 1700. These experimental results indicated that the system was not only highly accurate in delivering feed, but was also highly reliable in the transmission of information, and therefore met the production requirements of an intensive gestation house.

Coal-to-oil (CTL) combined with carbon capture, utilization and storage (CCUS) can significantly reduce the CO2 emissions generated in the production process to achieve clean coal utilization. Taking CTL enterprises as sources and deep saline aquifers and oil fields as sinks, this paper establishes a source–sink matching model, which is combined with a trinomial tree real-option model of carbon price fluctuation, and evaluates the investment decisions of CTL. The results show that 36 pipelines with an average transportation distance of 319.13 km and predominantly small diameters must be constructed for CO2 capture and storage combined with enhanced oil recovery (EOR). Under the current carbon price, 83.33% of enterprises can invest immediately when adopting EOR; when utilizing storage in a deep saline aquifer (DSF), even with a 50% subsidy and a decrease in costs due to the learning rate, enterprises still need to execute the deferred option investment. Government subsidies and technological advances can greatly increase the value of investment. The critical carbon price of CTL-CCUS projects is sensitive to government subsidies, technological advances, and CO2 transportation distances. Therefore, China should reasonably guide the development of the carbon market and give play to the role of the carbon market in emission reduction incentives. In addition, the Chinese government can provide direct financial support for the CTL-CCUS project to increase the enthusiasm of CTL enterprises for CCUS transformation and promote technological progress.

As the largest carbon emitter in China’s manufacturing sector, the low-carbon transition of the steel industry is urgent. CO2 capture, utilization, and storage (CCUS) technology is one of the effective measures to reduce carbon emissions in steel industry. In this paper, a comprehensive assessment model of source–sink matching-levelized cost in China’s steel industry is constructed to evaluate the potential, economy, and spatial distribution of CCUS retrofits of blast furnaces in the BF-BOF steel industry. The results show that, if no extra incentive policy is included, the levelized cost of carbon dioxide (LCOCD) of 111 steel plants with a 420.07 Mt/a CO2 abatement potential ranges from −134.87 to 142.95 USD/t. The levelized cost of crude steel (LCOS) range of steel plants after the CCUS retrofits of blast furnaces is 341.81 to 541.41 USD/t. The incentives such as carbon market and government subsidies will all contribute to the early deployment of CCUS projects. The CCUS technology could be prioritized for deployment in North China, Northwest China, and East China’s Shandong Province, but more powerful incentives are still needed for current large-scale deployment. The research results can provide references for the early deployment and policy formulation of CCUS in China’s steel industry.

Integral field spectroscopy (IFS) is capable of simultaneously collecting two-dimensional high-resolution spatial image information and spectral information in a target field of view (FOV). The image slicer is the key element in IFS for segmenting the target FOV. Current micro-image slicer fabrication methods such as molecular assembling need strictly accurate control during sticking, which is time-consuming and expensive. In this study, we improved a direct-adhesive method for thin glass slicer manufacture and alignment. Thin glass is fabricated via single polishing and direct stitching to form a micro-image slicer. Based on charge coupled device (CCD) camera tests on parallel light, the manufacture accuracy for a six-channel image slicer reaches that of the molecular assembling scheme. This method can be applied to the fabrication of image slicers with different apertures.

Abstract Background Several studies have revealed that N6-methyladenosine (m6A) regulation is involved in various biological processes and cancer progression. Nevertheless, the potential effects of m6A modifications in the tumor immune microenvironment (TIME) and on immune regulation in pancreatic adenocarcinoma (PAAD) remains unclear. Methods A consensus clustering algorithm was used to identify different m6A modification patterns and construct an m6A-associated gene signature based on 23 m6A regulators in PAAD. The CIBERSORT and ssGSEA algorithms were used to estimate the components of the immune cells in each sample. The PCA algorithm was used to develop the m6Ascore system for the evaluation of m6A modification patterns in each sample. Results Two m6A modification patterns with different biological properties and prognoses were identified in 176 PAAD patient samples. The features of TIME between the two patterns were similar, with two definite immune phenotypes: immune-inflamed and immune-excluded. Based on the m6A phenotype-associated signature genes, we constructed an m6Ascore system to investigate the m6A modification pattern of each sample, profile the dissection of physiological processes, immune infiltration, clinical prognosis, immunotherapy, and genetic variation. Patients with low m6Ascore scores had better clinical outcomes, enhanced immune infiltration, and lower expression of immunotherapeutic drug targets, such as CD274 and PDCD1LG2. Further research indicated that the m6Ascore and tumor mutation burden were significantly correlated, and patients with low m6Ascore had higher mutation rates in SMAD4 and TTN. Moreover, TNFRSF21 was significantly upregulated in PAAD tumor tissues and cell lines. Lower expression of TNFRSF21 had a prominent advantage in survival and was correlated with a low level of immune infiltration. PAAD samples with different TNFRSF21 expression levels showed significantly distinct sensitivities to chemotherapeutic agents. Conclusions This study revealed that m6A modification patterns could play an important role in the diversity and complexity of TIME, and the m6Ascore system could serve as an independent and powerful prognostic biomarker and is latently related to PAAD immunotherapies. Quantitative determination of m6A modification patterns in individual patients will be instrumental in mapping the TIME landscape and further optimizing precision immunotherapy.

RationaleCOVID-19 pandemic has imposed tremendous stress and burden on the economy and society worldwide. There is an urgent demand to find a new model to estimate the deterioration of patients inflicted by Omicron variants.ObjectiveThis study aims to develop a model to predict the deterioration of elderly patients inflicted by Omicron Sub-variant BA.2.MethodsCOVID-19 patients were randomly divided into the training and the validation cohorts. Both Lasso and Logistic regression analyses were performed to identify prediction factors, which were then selected to build a deterioration model in the training cohort. This model was validated in the validation cohort.Measurements and main resultsThe deterioration model of COVID-19 was constructed with five indices, including C-reactive protein, neutrophil count/lymphocyte count (NLR), albumin/globulin ratio (A/G), international normalized ratio (INR), and blood urea nitrogen (BUN). The area under the ROC curve (AUC) showed that this model displayed a high accuracy in predicting deterioration, which was 0.85 in the training cohort and 0.85 in the validation cohort. The nomogram provided an easy way to calculate the possibility of deterioration, and the decision curve analysis (DCA) and clinical impact curve analysis (CICA)showed good clinical net profit using this model.ConclusionThe model we constructed can identify and predict the risk of deterioration (requirement for ventilatory support or death) in elderly patients and it is clinically practical, which will facilitate medical decision making and allocating medical resources to those with critical conditions.

ObjectiveThe aim of the present study is to assess the utility of C-reactive protein to Lymphocyte Ratio (CLR) in predicting short-term clinical outcomes of patients infected by SARS-CoV-2 BA.2.2.MethodsThis retrospective study was performed on 1,219 patients with laboratory-confirmed SARS-CoV-2 BA.2.2 to determine the association of CLR with short-term clinical outcomes. Independent Chi square test, Rank sum test, and binary logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with their 95% CI, respectively.ResultsOver 8% of patients admitted due to SARS-CoV-2 BA.2.2. were critically ill. The best cut-off value of CLR was 21.25 in the ROC with a sensitivity of 72.3% and a specificity of 86%. After adjusting age, gender, and comorbidities, binary logistic regression analysis showed that elevated CLR was an independent risk factor for poor short-term clinical outcomes of COVID-19 patients.ConclusionC-reactive protein to Lymphocyte Ratio is a significant predictive factor for poor short-term clinical outcomes of SARS-CoV-2 BA.2.2 inflicted patients.

ABSTRACT: The purpose of this study was to investigate the effects of coating technology on the cysteamine (CSH) release in the digestive tract and the growth-promoting effect of enteric-coating CSH in broilers. First, using the self-developed computer-controlled simulated digestion system to mimic the digestion process in vitro, the release of 2 coated CSH (CSH-I and CSH-Ⅱ) were studied. The results showed that less than 10% of CSH-I was released after gastric digestion and 52.35% of CSH-I was released with additional 4 h of small intestinal digestion. In contrast, 83.62% of CSH-Ⅱ was released during the gastric digestion. In order to verify the growth-promoting effects of CSH-I, a feeding trial was conducted in a completely randomized block arrangement with 3 treatments in 6 blocks, 5 chickens per replicate. Broilers were fed with corn-soybean meal diet either supplemented with 0 (CON), 200 mg/kg uncoated CSH (CSH) or 200 mg/kg CSH-I from d 7 to 42, respectively. Body weight and FI was recorded at d 21 and 42. Excreta were collected from d 39 to d 42 to determine the total tract retention (TTR) of dietary nutrients. In comparisons with controls, birds fed with CSH-I had greater BW, ADG, and ADFI and increased TTR of DM, gross energy (GE), NDF and hemicellulose (P < 0.05). In addition, duodenal villi height and surface area were also greater in those CSH-I-fed birds. In contrast, the growth performance of birds fed with uncoated CSH did not significantly differ from controls. Although the TTR of DM and GE was higher in birds fed with CSH than controls, no differences in small intestine morphology were noted. Thus, the type I coating (CSH-I) could be good enteric-coating technology to increase CSH release in the duodenum, improve digestion and duodenal morphology, and therefore growth performance in broilers.

ObjectiveBy identifying the clinicopathological characteristics and prognostic influences of patients with triple-positive breast cancer (TPBC) at Xijing Hospital in China compared with those in the United States, this study aims to construct a nomogram model to forecast the overall survival rate (OS) of TPBC patients.MethodThe Surveillance, Epidemiology, and End Results (SEER) database was used to screen 5769 patients as the training cohort, and 191 patients from Xijing Hospital were used as the validation cohort. Cox risk-proportional model was applied to select variables and the nomogram model was constructed based on the training cohort. The performance of the model was evaluated by calculating the C-index and generating calibration plots in the training and validation cohorts.ResultsCox multifactorial analysis showed that age, chemotherapy, radiotherapy, M-stage, T-stage, N-stage, and the mode of surgery were all independent risk factors for the prognosis of TPBC patients (all P

The WDR45 encodes a beta-propeller scaffold protein which leads to β-propeller protein-associated neurodegeneration (BPAN) with iron accumulation in the brain. Using episomal reprogramming approach, we generated an iPSC line from peripheral blood mononuclear cells (PBMCs) from a 9-year-old girl with a non-canonical splice site c.344 + 5G > T in the WDR45 gene. The iPSC line had been fully examined about pluripotency marker, karyotype, and three germ layer differentiation.

Heat stress (HS) can be detrimental to the gut health of swine. Many negative outcomes induced by HS are increasingly recognized as including modulation of intestinal microbiota. In turn, the intestinal microbiota is a unique ecosystem playing a critical role in mediating the host stress response. Therefore, we aimed to characterize gut microbiota of pigs’ exposure to short-term HS, to explore a possible link between the intestinal microbiota and HS-related changes, including serum cytokines, oxidation status, and intestinal epithelial barrier function. Our findings showed that HS led to intestinal morphological and integrity changes (villus height, serum diamine oxidase [DAO], serum D-lactate and the relative expressions of tight junction proteins), reduction of serum cytokines (interleukin [IL]-8, IL-12, interferon-gamma [IFN-γ]), and antioxidant activity (higher glutathione [GSH] and malondialdehyde [MDA] content, and lower superoxide dismutase [SOD]). Also, 16S rRNA sequencing analysis revealed that although there was no difference in microbial α-diversity, some HS-associated composition differences were revealed in the ileum and cecum, which partly led to an imbalance in the production of short-chain fatty acids including propionate acid and valerate acid. Relevance networks revealed that HS-derived changes in bacterial genera and microbial metabolites, such as Chlamydia, Lactobacillus, Succinivibrio, Bifidobacterium, Lachnoclostridium, and propionic acid, were correlated with oxidative stress, intestinal barrier dysfunction, and inflammation in pigs. Collectively, our observations suggest that intestinal damage induced by HS is probably partly related to the gut microbiota dysbiosis, though the underlying mechanism remains to be fully elucidated.

There are many small objects in UAV images, and the object scale varies greatly. When the SSD algorithm detects them, the backbone network’s feature extraction capabilities are poor; it does not fully utilize the semantic information in the deeper feature layer, and it does not give enough consideration to the little items in the loss function, which result in serious missing object detection and low object detection accuracy. To tackle these issues, a new algorithm called RSAD (Resnet Self-Attention Detector) that takes advantage of the self-attention mechanism has been proposed. The proposed RSAD algorithm utilises the residual structure of the ResNet-50 backbone network, which is more capable of feature extraction, in order to extract deeper features from UAV image information. It then utilises the SAFM (Self-Attention Fusion Module) to reshape and concatenate the shallow and deep features of the backbone network, selectively weighted by attention units, ensuring the efficient fusion of features to provide rich semantic features for small object detection. Lastly, it introduces the Focal Loss loss function, which adjusts the corresponding parameters to enhance the contribution of small objects to the detection model. The ablation experiments show that the mAP of RSAD is 10.6% higher than that of the SSD model, with SAFM providing the highest mAP enhancement of 7.4% and ResNet-50 and Focal Loss providing 1.3% and 1.9% enhancements, respectively. The detection speed is only reduced by 3FPS, but it meets the real-time requirement. Comparison experiments show that in terms of mAP, it is far ahead of Faster R-CNN, Cascade R-CNN, RetinaNet, CenterNet, YOLOv5s, and YOLOv8n, which are the mainstream object detection models; In terms of FPS, it slightly inferior to YOLOv5s and YOLOv8n. Thus, RSAD has a good balance between detection speed and accuracy, and it can facilitate the advancement of the UAV to complete object detection tasks in different scenarios.

In the healing of wounds, human-like collagen (hCol) is essential. However, collagen-based composite dressings have poor stability in vivo, which severely limits their current therapeutic potential. Based on the above, we have developed a recombinant fusion protein named hCol-ELP, which consists of hCol and an elastin-like peptide (ELP). Then, we examined the physicochemical and biological properties of hCol-ELP. The results indicated that the stability of the hCol-ELP fusion protein exhibited a more compact and homogeneous lamellar microstructure along with collagen properties, it was found to be significantly superior to the stability of free hCol. The compound hCol-ELP demonstrated a remarkable capacity to induce the proliferation and migration of mouse embryo fibroblast cells (NIH/3T3), as well as enhance collagen synthesis in human skin fibroblasts (HSF) when tested in vitro. In vivo, hCol-ELP demonstrated significant enhancements in healing rate and a reduction in the time required for scab removal, thereby exhibiting a scar-free healing effect. The findings provide a crucial theoretical foundation for the implementation of an hCol-ELP protein dressing in fields associated with the healing of traumatic injuries.

Abstract Background To reveal the changes of intestinal microbial abundance and composition, as well as the microbiota metabolic levels of bile acids and short chain fatty acids of healthy preschool children during their growth. Methods Feces of 120 healthy newborns and 150 healthy children aged 6 months to 6 years were collected. Then the composition of intestinal flora was analyzed by 16S rRNA, and the contents of bile acids and short chain fatty acids in feces were detected by LC-MS and GS methods, respectively. Results The composition and function of intestinal microflora were not stable in neonatal period but significantly improved at 6 months after birth, and gradually stabilized and tended to adult-like formation after 2–3 years old. The levels of short chain fatty acids and secondary bile acids were consistent with the development of gut microbiota. Conclusion The age of 6 months may be a critical period for the development of intestinal microflora in children.

Abstract Objective The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode. Methods A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Results There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI − 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, − 0.07; 95% CI − 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, − 1.14; 95% CI − 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, − 2.51; 95% CI − 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28–30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62). Conclusion Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding. Trial registration number PROSPERO (CRD42021234581).

The intramuscular subtype of nodular fasciitis (NF) is rare with lesions normally not more than 2 cm in size and characterized by pseudosarcomatous morphology. We report a case of a 27-year-old man with a large-size intramuscular NF. The patient came for treatment complaining of an increasingly enlarged mass in the left upper arm for 4 months. Magnetic resonance imaging (MRI) confirmed the presence of a well-defined tumor measuring 5 cm within the outer edge of the middle humerus. Microscopically, the neoplasm was rich in fibroblasts and myofibroblasts in an interlaced pattern with high mitotic index and evident multinuclear giant cells. Erythrocyte extravasation was easily seen in the stroma. The tumor border was infiltrative. Immunohistochemically, the tumor cells were positive for smooth muscle actin (SMA) and negative for cytokeratin, desmin, H-Caldesmon, CD34, S100, ALK, and β-catenin. Fibrosarcoma was highly suspected by histopathological and immunohistochemical examination. Molecular detection demonstrated evidence of ubiquitin-specific peptidase 6 (USP6) gene rearrangement in this tumor. Based on the findings, the tumor was diagnosed as intramuscular NF. At 56 months after the initial surgery, the patient had recovered with no evidence of recurrence or metastasis. Large-size intramuscular NF is very rare and easily overdiagnosed as malignant tumor due to its obvious pseudosarcomatoid pathological features. USP6 gene rearrangement detection can effectively avoid this major misdiagnosis.

IntroductionNumerous studies have reported the modification of particulate matters (PMs) on the association between cold temperature and health. However, it remains uncertain whether the modification effect may vary by size of PMs, especially in Shandong Province, China where the disease burdens associated with cold temperature and PMs are both substantial. This study aimed to examine various interactive effects of cold exposure and ambient PMs with diameters ≤1/2.5 μm (PM1 and PM2.5) on premature deaths in Shandong Province, China.MethodsIn the 2013-2018 cold seasons, data on daily mortality, PM1 and PM2.5, and weather conditions were collected from the 1822 sub-districts of Shandong Province. A time-stratified case-crossover study design was performed to quantify the cumulative association between ambient cold and mortality over lag 0-12 days, with a linear interactive term between temperature and PM1 and PM2.5 additionally added into the model.ResultsThe mortality risk increased with temperature decline, with the cumulative OR of extreme cold (−16.9°C, the 1st percentile of temperature range) being 1.83 (95% CI: 1.66, 2.02), compared with the minimum mortality temperature. The cold-related mortality risk was 2.20 (95%CI: 1.83, 2.64) and 2.24 (95%CI: 1.78, 2.81) on high PM1 and PM2.5 days, which dropped to 1.60 (95%CI: 1.39, 1.84) and 1.60 (95%CI: 1.37, 1.88) on low PM1 and PM2.5 days. PM1 showed greater modification effect for per unit concentration increase than PM2.5. For example, for each 10?g/m3 increase in PM1 and PM2.5, the mortality risk associated with extreme cold temperature increased by 7.6% (95% CI: 1.3%, 14.2%) and 2.6% (95% CI: −0.7%, 5.9%), respectively.DiscussionThe increment of smaller PMs' modification effect varied by population subgroups, which was particularly strong in the elderly aged over 75 years and individuals with middle school education and below. Specific health promotion strategies should be developed towards the greater modification effect of smaller PMs on cold effect.

Aerial ammonia exposure leads to tissue damage and metabolic dysfunction. However, it is unclear how different organs are coordinated to defend against aerial ammonia exposure. Twenty-four pigs were randomly divided into 4 groups, exposed to 0, 10, 25 or 35 mg/m3 ammonia respectively for 25 d. After above 25 mg/m3 ammonia exposure, decreased aspartate (P = 0.016), glutamate (P = 0.030) and increased ornithine (P = 0.002) were found in the ammonia-removing liver, and after high ammonia (35 mg/m3) exposure, glutamine synthetase (GS) expression was increased (P = 0.012). An increased glutamate (P = 0.004) and decreased glutaminase (GLS) expression (P = 0.083) were observed in the lungs after high ammonia exposure. There was also an increasing trend of glutamine in the kidneys after high ammonia exposure (P = 0.066). For branched-chain amino acid (BCAA) catabolism, high ammonia exposure increased BCAA content in both the lungs and muscle (P

Abstract In order to solve the problem of uncontrollable cutting depth and the rough incision edge of the cornea with manual trephine in lamellar keratoplasty, an ultrasonic‐assisted corneal trephination method has been proposed for the first time in accordance with the advantage of ultrasonic vibration cutting, and the corresponding robotic system has been designed and researched. According to the traditional process of lamellar keratoplasty, the requirements of the surgical robotic system were first proposed. On this basis, the robotic system was designed and its schematic diagram was introduced. Second, the key components of the robotic body such as the eccentric adjusting mechanism and the end‐effector of ultrasonic scalpel were illustrated, which can realise corneal trephination of different incision diameters without scalpel replacement. Then the operation flow chart of a robot‐assisted lamellar keratoplasty was put forward. Finally, the preliminary verified experiments were performed using a grape and a porcine eyeball, respectively, in vitro with the prototype system. The results show that the robotic system can basically satisfy the operation requirements of lamellar keratoplasty. Owing to the less cutting force and smoother corneal incision edge of ultrasonic‐assisted lamellar keratoplasty compared with manual trephine, it was proved to be more feasible and superior.

The blending behavior of aged and virgin asphalt binder is one of the most critical problems in the mixing process of hot recycling. To accurately measure the participation degree of aged asphalt and optimize the mixing process of hot recycling, a series of laboratory tests were designed by using magnetite aggregate and thin-layer chromatography with flame ionization detection (TLC-FID) for the first time. In this study, 24 different lab-mixing conditions were deliberately adopted to investigate the impact on the DoB of aged and virgin asphalt binders, including mixing amount of RAP, mixing amount of rejuvenating agent, mixing time, mixing temperature, mixing orders and the thickness of asphalt film. The results indicated that the aged and virgin asphalt cannot be completely blended in the mixing process and DoB is only about 40–60 % in general. The DoB decreases with the increase of asphalt film thickness and it decreases by 30 % when asphalt film thickness is 9 µm. DOB increased with the content of RAP and rejuvenating agent up to 70 % which same as mixing sequence. Although the mixing time and temperature can promote DOB, the mixing time and temperature should be controlled within 240 s and 170 °C, otherwise the accuracy of DOB will be affected.

Objective To analyze the causes and treatments for the incompatible crossmatching between a patient, who underwent the minor ABO mismatches lung transplantation, and the blood donor with ABO-compatible blood. Methods A patient, who underwent the minor ABO mismatches (donor group O; recipient group A) lung transplantation developed a continuous decrease in Hb for 13 days after surgery, The blood sample of the patient presented major crossmatching incompatibility with the blood donors and the causes of it were analyzed by the recipient′s blood type reviewing, direct antiglobulin test, antibody screening and erythrocyte elution. Results The patient’s serum reacted with A1 erythrocyte reagent with agglutination strength at ±, and enhanced to 1+ at 4℃ after 10 min incubation.Antibodies were not detected by 10-cell panel and the effects of unexpected antibodies were excluded.The results of direct antiglobulin test and elution test were positive, and eluted anti-A antibody was detected.Combined with the patient′s continuous decline in Hb and elevated total bilirubin, passenger lymphocyte syndrome (PLS) was clinically diagnosed.After the transfusion of 6 U of O-type washed RBCs, the symptoms of anemia were improved and no adverse reactions occurred. Conclusion PLS may occur after an ABO mismatched solid organ transplantation.Most of the hemolytic symptoms are not obvious and easy to ignore, therefore clinical indicators of direct antiglobulin test results, Hb and total bilirubin should be continuously monitored after transplantation for early detection and timely treatment of PLS to avoid major adverse consequences.

Background: Cavernous nerve injury (CNI) is the leading cause of erectile dysfunction (ED) after radical prostatectomy and pelvic fracture. Transplantation of human adipose-derived stem cells (ASCs) has been widely used to restore erectile function in CNI-ED rats and patients. Umbilical cord blood-derived MSCs (CBMSCs) are similarly low immunogenic but much primitive compared to ASCs and more promising in large-scale commercial applications due to the extensive establishment of cord blood banks. However, whether CBMSCs and ASCs have differential therapeutic efficacy on CNI-ED and the underlying mechanisms are still not clear.Materials and methods: A bilateral cavernous nerve injury (BCNI) rat model was established by crushing the bilateral cavernous nerves. After crushing, ASCs and CBMSCs were intracavernously injected immediately. Erectile function, Masson staining, and immunofluorescence analyses of penile tissues were assessed at 4 and 12 weeks. PKH-26-labeled ASCs or CBMSCs were intracavernously injected to determine the presence and differentiation of ASCs or CBMSCs in the penis 3 days after injection. In vitro experiments including intracellular ROS detection, mitochondrial membrane potential assay, EdU cell proliferation staining, cell apoptosis assay, and protein chip assay were conducted to explore the underlying mechanism of CBMSC treatment compared with ASC treatment.Results: CBMSC injection significantly restored erectile function, rescued the loss of cavernous corporal smooth muscles, and increased the ratio of smooth muscle to collagen. PKH-26-labeled CBMSCs or ASCs did not colocalize with endothelial cells or smooth muscle cells in the corpus cavernosum. Moreover, the conditioned medium (CM) of CBMSCs could significantly inhibit the oxidative stress and elevate the mitochondria membrane potential and proliferation of Schwann cells. Better therapeutic effects were observed in the CBMSC group than the ASC group both in vivo and in vitro. In addition, the content of neurotrophic factors and matrix metalloproteinases in CBMSC-CM, especially NT4, VEGF, MMP1, and MMP3 was significantly higher than that of ASC-CM.Conclusion: Intracavernous injection of CBMSCs exhibited a better erectile function restoration than that of ASCs in CNI-ED rats owing to richer secretory factors, which can promote nerve regeneration and reduce extracellular matrix deposition. CBMSC transplantation would be a promising therapeutic strategy for CNI-ED regeneration in the future.

The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy.

BackgroundPost-stroke cognitive impairment (PSCI) after lacunar infarction was worth attention in recent years. An easy-to-use score model to predict the risk of PSCI was rare. This study aimed to explore the association between serum amyloid A (SAA) and cognitive impairment, and it also developed a nomogram for predicting the risk of PSCI in lacunar infarction patients.MethodsA total of 313 patients with lacunar infarction were enrolled in this retrospective study between January 2021 and December 2021. They were divided into a training set and a validation set at 70%:30% randomly. The Chinese version of the Mini-Mental State Examination (MMSE) was performed to identify cognitive impairment 3 months after discharge. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for PSCI in the training set. A nomogram was developed based on the five variables, and the calibration curve and the receiver operating characteristic (ROC) curve were drawn to assess the predictive ability of the nomogram between the training set and the validation set. The decision curve analysis (DCA) was also conducted in both sets.ResultsIn total, 52/313 (16.61%) participants were identified with PSCI. The SAA levels in patients with PSCI were significantly higher than non-PSCI patients in the training set (P < 0.001). After multivariate analysis, age, diabetes mellitus, white blood count, cystatin C, and SAA were independent risk predictors of PSCI. The nomogram demonstrated a good discrimination performance between the training set (AUC = 0.860) and the validation set (AUC = 0.811). The DCA showed that the nomogram had a well clinical utility in the two sets.ConclusionThe increased SAA is associated with PSCI in lacunar infarction patients, and the nomogram developed with SAA can increase prognostic information for the early detection of PSCI.

ABSTRACT: The objective of this study was to compare the digestibility of energy and fatty acids (FA) in rice bran oil (RBO) and palm oil (PO) fed to growing Arbor Acre (AA) broilers. A corn-soybean meal basal diet and the basal diet supplemented with 8% RBO or PO were evaluated. A total of 72 AA male broilers (initial BW = 1,173 ± 6 g; age = 22 d) were randomly divided to 3 dietary treatments with 6 replicates of 4 broilers in each. The growth performance and the ME and FA digestibility in oils were compared with a balance experiment of broilers from d 22 to 28. The ME of the RBO diet was greater (P < 0.05) than PO diet and basal diet, and the ME of the PO diet was greater (P < 0.05) than basal diet. However, no statistical difference was observed in the ME intake of broilers fed basal, RBO, and PO diets. To maintain daily ME intake, broilers ingested more basal diet relative to other diets, resulting in increased CP intake (P < 0.01) and retention (P < 0.01) than broilers fed diets supplemented with RBO and PO. This finding resulted in greater (P < 0.01) BWG and ADG from d 22 to 28 for broilers fed the basal diet relative to other diets, but there was no difference for BWG and ADG across oil sources. However, broilers fed RBO had numerically greater BWD and ADG than those fed PO, likely because the RBO provided greater AME, AMEn, AME/GE, AMEn/GE (P < 0.01) as well as ether extract (EE) digestibility (P = 0.0536) relative to PO. The digestibility of palmitic (C16:0), stearic (C18:0), oleic (C18:1), and linoleic (C18:2) were greater (P < 0.01) in RBO than PO, which positively influenced the energy values for RBO. These results indicate RBO has greater ME and digestibility of EE and FA, which positively influenced the growth performance of AA broilers. Therefore, RBO can be used to replace PO in broiler diets.

PurposeCuprotosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by copper-dependent and associated with mitochondrial respiration. However, the prognostic significance and function of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are unknown. This study aims to develop cuprotosis-mediated patterns-related gene (CMPRG) prediction models for the prognosis of patients with HCC, exploring the functional underlying the CRGs on the influence of tumor microenvironment (TME) features.Experimental designThis study obtained transcriptome profiling and the corresponding clinical information from the TCGA and GEO databases. Besides, the Cox regression model with LASSO was implemented to build a multi-gene signature, which was then validated in an internal validation set and two external validation sets through Kaplan-Meier, DCA, and ROC analyses.ResultsAccording to the LASSO analysis, we screened out a cuprotosis-mediated pattern 5-gene combination (including PBK; MMP1; GNAZ; GPC1 and AKR1D1). A nomogram was constructed for the presentation of the final model. The ROC curve assessed the model’s predictive ability, which resulted in an area under the curve (AUC) values ranging from 0.604 to 0.787 underwent internal and two external validation sets. Meanwhile, the risk score divided the patients into two groups of high and low risk, and the survival rate of high-risk patients was significantly lower than that of low-risk patients (P

In the present work, a nanofibrous Fe-N/C catalyst with a multi-scaled porous structure is proposed and prepared via electrospinning a polyacrylonitrile (PAN) solution containing Fe3+ incorporated graphitic carbon nitride (Fe-g-C3N4). Physical and chemical characterizations confirm that micropores, mesopores and hollow-out macropores are co-existed in the Fe-N/C nanofibrous catalysts. The abundant micropores are beneficial for accommodating active sites, while the mesopores and hollow-out macropores can facilitate the supply of oxygen to the active surfaces. Moreover, due to the fibrous morphology of the catalyst, a 3D highly-porous electrode with well-established networks can be formed for facile transport of electrons and oxygen. The experimental results show that the Fe-N/C catalyst delivers a good activity toward oxygen reduction reaction (ORR) in acid media with a half-wave potential of 740 mV and an almost four-electron transfer process, high stability and excellent methanol tolerance. Furthermore, the as-prepared catalyst is used to fabricate the cathode of a direct methanol fuel cell, which yields a peak power density of 14.9 mW cm-2 with 1 M methanol solutions, dry air and an operating temperature of 70°C. [ABSTRACT FROM AUTHOR]

Based on ship navigational requirements and safety in foggy conditions and with a particular emphasis on avoiding ship collisions and improving navigational abilities, we constructed a fog navigation dataset along with a new method for enhancing foggy images and perceived visibility using a discriminant deep learning architecture and the EfficientNet neural network by replacing the SE module and incorporating a convolution block attention module and focal loss function. The accuracy of our model exceeded 95%, which meets the needs of an intelligent ship navigation environment in foggy conditions. As part of our research, we also determined the best enhancement algorithm for each type of fog according to its classification.

Abstract Background C-Myc aberrations confer a more aggressive clinic behavior in diffuse large B-cell lymphoma (DLBCL). Matrine is an alkaloid extracted from Sophora flavescens Ait. It possesses anti-cancer property through inhibiting the cell proliferation and inducing the apoptosis. The present study aimed to explore the underlying mechanisms of matrine in suppressing the cell growth of DLBCL. Methods The influence of matrine on the viability of cultured DLBCL cell lines SU-DHL-16 and OCI-LY3 cells were determined by CCK-8. Apoptosis and cell cycle were measured by flow cytometry after matrine exposure. Western blot was taken to investigate the expression of activated Caspase-3, cleaved PARP, c-Myc, phospho-c-Myc (Ser62), CaMKIIγ, phospho-CaMKIIγ (Thr287), CDK4 and CDK6 after matrine treatment. Cycloheximide chase analysis was used to determine the c-Myc protein half-lives before and after matrine treatment. Growth salvage analysis was taken by ectopic expression of c-Myc. Results In cultured DLBCL cells, matrine suppressed cell viability in a concentration and time dependent fashion. Matrine treated SU-DHL-16 and OCI-LY3 cells for 48 h with IC50 value of 1.76 mM and 4.1 mM, respectively. Matrine induced apoptosis through a caspase-independent pathway and caused G0/G1 cell cycle arrest in a concentration dependent manner in DLBCL cells. The protein expression of c-Myc was inhibited while the transcription of c-Myc was not reduced by matrine. c-Myc protein half-lives were decreased from 30.4, 69.4 min to 16.6, 15.9 min after matrine treatment in SU-DHL-16 and OCI-LY3, respectively. As a critical protein kinase of c-Myc, CaMKIIγ phosphorylation at Thr287 was found to be down-regulated and c-Myc phosphorylation at Ser62 was reduced together after matrine treatment in DLBCL. The growth suppression of SU-DHL-16 cells induced by matrine was rescued by over-expression of c-Myc achieved by recombinant adenovirus infection. The decreased expression of CDK6, not CDK4, induced by matrine was rescued by ectopic expression of c-Myc protein. Conclusions This study has shown for the first time that matrine suppresses cell growth of DLBCL via inhibiting CaMKIIγ/c-Myc/CDK6 signaling pathway.

Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.

Background and ObjectiveBone erosion is common in patients with gout. The role of neutrophil-derived exosomes in gouty bone erosion remains elusive. This study aimed to investigate the functions of the neutrophil-derived exosomes in the development of bone erosion in gout.MethodsNeutrophil-derived exosomes were collected and assessed by transmission electron microscopy and nanoparticle tracking analysis. Cell counting kit-8 assay was applied to evaluate cell viability, and cell apoptosis was assessed by flow cytometry. In addition, quantitative Real-time PCR and Western blotting were used to determine the expression levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL). Neutrophil-derived exosomes were tagged with PKH67. The miRNA expression profiles of exosomes and human fetal osteoblasts (hFOB) were compared using high-throughput sequencing. Functional miRNAs transfected into hFOB after co-incubation with exosomes were selected and validated by preliminary qPCR.ResultsNeutrophil-derived exosomes were stimulated by monosodium urate (MSU). The exosomes could inhibit the viability of the hFOB, and the expression levels of ALP and OPG were down-regulated, while the expression level of RANKL was up-regulated. However, there was no significant difference in the viability of osteoclasts and the expression of nuclear factor of activated T cells 1. Exosomes were observed in the cytoplasm under a confocal microscopy, confirming that exosomes could be taken up by hFOB. In total, 2590 miRNAs were found, of which 47 miRNAs were differentially expressed. Among the delivered miRNAs, miR-1246 exhibited the highest level of differential expression. The viability of hFOB was reduced by miR-1246 mimics and increased by miR-1246 inhibitors. There was no significant difference in hFOB apoptosis rate between the miR-1246 mimic and miR-1246 inhibitor group. MiR-1246 overexpression decreased the expression levels of ALP and OPG, whereas increasing the expression level of RANKL. In contrast, miR-1246 inhibitor increased the expression levels of ALP and OPG, while decreasing the expression level of RANKL. Neutrophil-derived exosomes stimulated by MSU could increase the expression of miR-1246. ConclusionNeutrophil-derived exosomes stimulated by MSU could inhibit the viability of osteoblasts.

Abstract. Introduction:. When initiating urate-lowering therapy, using anti-inflammatory prophylaxis therapy for at least 3 to 6 months is strongly recommended. Previous studies have found that zhengqing fengtongning sustained-release tablets (sinomenine) can improve inflammation in the acute phase of gout; however, the efficacy of urate-lowering therapy in reducing frequency of acute flares still needs to be investigated. The aim of the present study is to explore the efficacy and safety of sinomenine for prophylaxis of acute flares when initiating urate-lowering therapy. Methods and analysis:. This randomized, placebo-controlled, double-blinded trial will include a total of 210 gout patients who meet the study criteria. The patients will be randomized (1:1) to the test group and the control group. The intervention is planned to be performed for 12 weeks with a follow-up of 12 weeks. All patients would be administered febuxostat (40 mg/d) and concomitant anti-inflammatory prophylaxis therapy. Sinomenine and colchicine placebo are administered in the sinomenine group, sinomenine placebo and colchicine are administered in the colchicine group. The primary outcome is the rate of acute gout flares in subjects within 12 weeks of the treatment period. The secondary outcomes include the times of acute gout flares and the duration of each acute flares within 12 weeks; the compliance rate in patients whose UA levels ≤6.0 mg/dL (360 μmol/L) at the weekend of 2nd, 4th, 8th, and 12th week in each group; the proportion of patients with ≥1 and ≥2 gout flares within 12 weeks; average visual analogue scale/score pain score during gout flares; and the oral dose of etoricoxib will be used to control the onset of acute flares within 12 weeks. Ethics and dissemination:. The Institutional Medical Ethics Committee have approved the trial protocol. We plan to publish the results of this study in a peer-reviewed journal. Trial registration:. ChiCTR, ChiCTR2100045114, Registered 8 April 2021 http://www.chictr.org.cn/showproj.aspx?proj=124688

Plain English summary The hippocampus is an area of the brain that is vital for memory and learning, and it is not understood the extent to which its function is impaired in anorexia nervosa (AN). This paper used the Mnemonic Similarity Task to assess pattern separation, a hippocampus-dependent form of memory, in AN. This task involves showing participants a sequence of objects, who then categorise them as “indoor” or “outdoor” objects. Participants are later shown a sequence of objects, although some of the images are replaced by a similar but slightly different image. The task involves recognising whether an image has previously been seen (pattern recognition) and also whether it is similar to, but distinct, from a previous image (i.e. pattern separation). In this study, individuals with AN showed reduced performance in pattern recognition, when statistically controlling for their age, how the task was delivered and their use of antidepressant medication. However, their performance in pattern separation was intact. This may indicate an imbalance in this hippocampus-dependent form of memory in AN.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown. Methods In the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF. Results CHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF. Conclusions Our work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL. Trial registration Not applicable.

Drought stress is a limiting factor for wheat production and food security. Drought priming has been shown to increase drought tolerance in wheat. However, the underlying mechanisms are unknown. In the present study, the genes encoding the biosynthesis and metabolism of abscisic acid (ABA) and jasmonic acid (JA), as well as genes involved in the ABA and JA signaling pathways were up-regulated by drought priming. Endogenous concentrations of JA and ABA increased following drought priming. The interplay between JA and ABA in plant responses to drought priming was further investigated using inhibitors of ABA and JA biosynthesis. Application of fluridone (FLU) or nordihydroguaiaretic acid (NDGA) to primed plants resulted in lower chlorophyll-fluorescence parameters and activities of superoxide dismutase and glutathione reductase, and higher cell membrane damage, compared to primed plants (PD) under drought stress. NDGA + ABA, but not FLU + JA, restored priming-induced tolerance, as indicated by a finding of no significant difference from PD under drought stress. Under drought priming, NDGA induced the suppression of ABA accumulation, while FLU did not affect JA accumulation. These results were consistent with the expression of genes involved in the biosynthesis of ABA and JA. They suggest that ABA and JA are required for priming-induced drought tolerance in wheat, with JA acting upstream of ABA.

Abstract Background The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity. Results In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria (“superbugs”) existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such “cutotypes” was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development. Conclusions The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome. Video abstract

According to the advantages of ultrasonic vibration cutting, an ultrasound-assisted corneal trepanation robotic system is developed to improve the accuracy of corneal trephination depth and corneal incision quality in corneal trephination operations. Firstly, we analyzed the reasons for the difficulty in controlling the depth of trephination in corneal transplantations from the perspective of the biomechanical properties of the cornea. Based on the advantages of ultrasonic vibration cutting, we introduced an ultrasonic-vibration-assisted cutting method for corneal trephination and analyzed the cutting mechanism. Secondly, we described the surgical demands of corneal trephination and listed the design requirements of a robotic system. Thirdly, we introduced the design details of said system, including the system’s overall structure, the ultrasound-assisted end effector, the key mechanisms of the robotic system, and the human–machine interaction interface. We designed the end effector based on ultrasonic vibration cutting and its eccentric adjustment system in an innovative way. Additionally, we then presented a procedure for robot-assisted corneal trephination. Finally, we performed several cutting experiments on grapes and porcine eyeballs in vitro. The results show that, compared with manual trephine, ultrasound-assisted corneal trephination has a better operation effect on the accuracy of corneal trephination depth and corneal incision quality.

The Huaibei grey donkey (HGD) is an endangered species and a vital native breed in Anhui Province, China. However, its complete mitogenome, phylogeny, and maternal origin remain unclear. The objectives of this study were to detect the genetic diversity of the HGD and investigate its phylogenetic relationship with other breeds to inform conservation management. The complete mitogenome of the HGD was sequenced through next-generation sequencing, and the most variable region in the mitochondrial DNA displacement-loop (D-loop) was amplified via a polymerase chain reaction (PCR). Next, we used the median-joining network (MJN) to calculate the genetic relationships among populations and the neighbor-jointing method to build a phylogenetic tree and speculate as to its origin. The results showed that the mitogenome contains 22 tRNAs, 2 rRNAs, 13 PCGs, and 1 D-loop region. Analyzing the D-loop region of the HGDs, we identified 23 polymorphic sites and 11 haplotypes. The haplotype and nucleotide diversity were 0.87000 (Hd) and 0.02115 (Pi), respectively. The MJN analysis indicated that the HGD potentially has two maternal lineages, and phylogenetic analysis indicated that the Somali lineage could be the most probable domestication center for this breed. Therefore, our mitogenome analysis highlights the high genetic diversity of the HGD, which may have originated from the Somali wild ass, as opposed to the Asian wild ass. This study will provide a useful resource for HGD conservation and breeding.