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Here, the effects of konjac glucomannan (KGM) and oligo-glucomannan (KOGM) on improving Aβ-induced Alzheimer’s disease (AD) was investigated. Behavioral test suggested that both KGM and KOGM could significantly increase the spatial learning and memory of AD mice, with the latter be more effective. Biochemical examinations revealed that KOGM inhibited the Aβ accumulation and hyperphosphorylation of Tau protein, upregulated bdnf, trkb, pi3k and akt, and downregulated gsk3β. Metagenomic sequencing indicated that KOGM regulated the diversity and function of microbiota, especially bacteria belonging to Alistipes, thus promoting the production of short chain fatty acids (SCFAs), as well as their cyclic levels. The strong relationships among gut microbiota, SCFAs and physiological index for AD suggested that KOGM could activated BDNF/PI3K/GSK3β pathway to ameliorate AD, by enhancing SCFAs levels. This study emphasized the KOGM as a potential prebiotic to prevent AD progression, through the gut-brain axis and constitutes a novel approach in AD treatment.

Methotrexate (MTX) is a therapeutic drug that is widely used in clinic for treatment of a variety of cancers. However, MTX has limited selectivity and serious cytotoxicity, at the same time, there are problems such as narrow therapeutic window and large individual variability in metabolism and excretion of MTX. Therefore, blood concentration monitoring is required for MTX administration in clinical practice. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has the advantages of strong specificity, good separation characteristics, high sensitivity and fast detection speed, which has become the internationally recognized “gold standard” for blood concentration monitoring of drugs. In this study, an isotope dilution mass spectrometry method was developed for accurate measurement of MTX in serum by the house-made QLIT-6610MD quadrupole-linear ion trap liquid chromatography-mass spectrometer. Unlike the traditional triple quadrupole QqQ tandem mass spectrometer, the quadrupole-linear ion trap (Q-LIT) mass spectrometer adopts the quadrupole-linear ion trap direct axial coupling design, i.e., a single linear ion trap is used to replace the QqQ tandem mass spectrometer’s back-end fragmentation cell and the quadrupole, and no other components are installed between the quadrupole and linear ion trap, which greatly streamlines the quality and efficiency of the mass spectrometer while ensuring the original performance of the instrument. With this unique configuration, the QLIT-6610MD instrument uses a simultaneous fragmentation and accumulation technique, which remarkedly reduces matrix-induced interferences and effectively reduces space charge effects. Serum samples were pretreated with methanol to precipitate proteins and the supernatants were measured by QLIT-6610MD spectrometer. The linear correlation coefficient (R2＞0.999 0) is obtained for MTX in the range of 10-5 000 μg/L. The limit of quantification is 10 μg/L. The precision of the quality control is better than 6.94%, and the recoveries of spiked serum samples are 86.39%-97.84% with a coefficient of variation less than 8.04%. We used the QLIT-6610MD and AB QTRAP 6500+ liquid chromatography-mass spectrometers to analyze 70 clinical serum samples for comparison of the performance of the house-made instrument by means of Pearson’s coefficient and BLand-ALtman method. The results showed that the QLIT-6610MD mass spectrometry achieves a similar level of performance to AB ATRAP 6500+ instrument, and provides a new domestic instrument option for clinical mass spectrometry. In addition, this study explores the possibility applying the multi-stage fragmentation technique (MSn) to determine MTX in serum, gaining fundamental data for future studies.

Abstract Background The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. Methods We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). Results The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. Conclusion These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Vetiver grass (Chrysopogon zizanioides) has received extensive attention in recent years due to its diverse applications in soil and water conservation, heavy metal remediation, as well as essential oil and phenolic acids extraction. In 2019, the emergence of tar spot disease on C. zizanioides was documented in Zhanjiang, Guangdong Province, China. Initially, the disease manifested as black ascomata embedded within leaf tissue, either scattered or clustered on leaf surfaces. Subsequently, these ascomata became surrounded by fisheye lesions, characterised by brown, elliptical, necrotic haloes, which eventually coalesced, resulting in leaf withering. Koch’s postulates demonstrated that the fungus isolated from these lesions was the causal agent. Microscopic examination showed that the pathogen morphologically belonged to Microdochium. The phylogenetic tree inferred from the combined ITS, LSU, tub2 and rpb2 sequences revealed the three isolates including GDMCC 3.683, LNU-196 and LNU-197 to be a novel species of Microdochium. Combining the results of phylogenetic, pathogenicity and morphological analyses, we propose a new species named M. chrysopogonis as the causal agent of C. zizanioides in southern China. The optimum growth temperature for M. chrysopogonis was determined to be 30 °C. The in vitro fungicide sensitivity of M. chrysopogonis was determined using a mycelial growth assay. Four demethylation-inhibiting (DMI) fungicides, including difenoconazole, flusilazole, propiconazole and tebuconazole and one methyl benzimidazole carbamate (MBC) fungicide, carbendazim, were effective against M. chrysopogonis, with mean 50% effective concentration (EC50) values of 0.077, 0.011, 0.004, 0.024 and 0.007 μg/ml, respectively. These findings provide essential references for the precise diagnosis and effective management of M. chrysopogonis.

Abstract Examining beta diversity of animal assemblages in fragmented habitats, which measures variation in species composition among different fragments, is important for understanding the impact of habitat fragmentation on biodiversity. However, relying solely on taxonomic composition may not provide a comprehensive understanding. Incorporating measures of functional and phylogenetic diversities is essential for elucidating the ecological mechanisms underlying changes in community composition. In addition, prevailing studies often prioritize the evaluation of landscape characteristics within fragments as determinants of beta diversity, neglecting differences in habitat type and plant community composition. In this study, we surveyed birds in 26 remnant woodlot patches (ranging from 0.3 to 290.4 ha) in an urban landscape, southwest China, during the breeding season from 2017 to 2022. We recorded 70 bird species (excluding those recorded only once and high‐flying birds, including raptors, swallows, and swifts), with the number of species per patch varying from 14 to 56. The overall bird taxonomic and phylogenetic beta diversities were primarily contributed by the turnover component, while functional beta diversity was dominated by the nestedness‐resultant component. Patch area and perimeter area ratio significantly influenced the taxonomic, functional, and phylogenetic beta diversities, primarily mediated through the nestedness‐resultant component, while inter‐patch distance had a significant effect via the turnover component. In addition, there was a considerable correlation of bird taxonomic, functional, and phylogenetic beta diversities with habitat type and woody plant beta diversities, including their respective partitioned turnover and nestedness‐resultant components. Our results suggest that bird assemblages in these patches may be regulated by selective extinction, interspecific competition, and environmental filtering. The findings have significant implications for sustainable landscape planning and habitat restoration. Conserving habitat patches of different sizes and maintaining or enhancing habitat heterogeneity between patches can facilitate the persistence of metacommunities.

Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating β-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis.

Abstract The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Because transformer plays an important role in power system, it rarely runs in fault or abnormal state. Therefore, it is difficult to obtain sufficient transformer fault samples. In this paper, aiming at the problem of less fault sample data and data imbalance, a novel data augmentation method based on kernel principal component analysis is proposed to non-linearly map the original data to a high-dimensional feature space. In this way, the new sample data retaining the feature information of the original data can be obtained. Second, the deep residual network is introduced with the identity path to construct the fault diagnosis model, which enables the weight parameters to be effectively transferred and updated. The simulation results show that the proposed method can effectively expand the data samples with high similarity with the original data, and the residual network model has strong feature extraction ability, which improves the accuracy of fault diagnosis.

Passive acoustic monitoring has been an effective tool for bird sound analysis. However, bird sounds often include cicada noise, which is an obstacle for investigating bird sounds. For example, cicada noise can result in large deviations of acoustic index, which will lead to the mismonitoring of species richness trends. Therefore, there is a critical need to filter cicada noise for helping bird sound analysis. We develop a novel end-to-end deep learning model, named CicadaNet for filtering cicada chorus from recordings containing bird sound. CicadaNet utilizes a convolutional encoder-decoder network to encode and decode acoustic features and a conformer module for global and local sequence modeling. We build a clean bird sound dataset and collect a large amount of real cicada noise data for model evaluation. We compare CicadaNet with current state-of-the-art deep denoising models and traditional denoising algorithms. Experimental results show that CicadaNet achieves the best denoising performance (SegSNR is improved by 9.59 dB and SI-SNR is improved by 20.08 dB when the noisy SNR = 0 dB). Meanwhile, CicadaNet achieves good performance for the real-time denoising of cicada noise. Furthermore, CicadaNet achieves bird species-independent noise reduction. We evaluate the effectiveness of CicadaNet for bird diversity survey. CicadaNet achieves the best performance, which can effectively eliminate the deviation caused by cicada noise to the acoustic index. CicadaNet can be easily extended to the cancellation of other environmental noise, and we propose it for the acoustic denoising of other vocalizing animals.

Bird sound classification plays an important role in large-scale temporal and spatial environmental monitoring. In this paper, we investigate both transfer learning and training from scratch for bird sound classification, where pre-trained models are used as feature extractors. Specifically, deep cascade features are extracted from various layers of different pre-trained models, which are then fused to classify bird sounds. A multi-view spectrogram is constructed to characterize bird sounds by simply repeating the spectrogram to make it suitable for pre-trained models. Furthermore, both mixup and pitch shift are applied for augmenting bird sounds to improve the classification performance. Experimental classification on 43 bird species using linear SVM indicates that deep cascade features can achieve the highest balanced accuracy of 90.94% ± 1.53%. To further improve the classification performance, an early fusion method is used by combining deep cascaded features extracted from different pre-trained models. The final best classification balanced accuracy is 94.89% ± 1.35%.

Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.

Objective: To initially explore traditional Chinese medicine patterns in a bleomycin-induced pulmonary fibrosis mouse model. Methods: Thirty-six C57BL/6 mice were divided by the random number table method (with 12 rats per group) into three groups: a blank group, a model group, and a number 2 Feibi recipe (FBR-2) group. The pulmonary fibrosis mouse model was established by intratracheal instillation of bleomycin. The FBR-2 group was treated with FBR-2 for 4 weeks. Symptoms in the mice such as mental behavior, food/water intake, body weight, body temperature, respiratory rate, and tongue image were observed. The samples were collected on the 14th day and 28th day after modeling, and lung tissues were visually assessed and microscopically evaluated by staining with hematoxylin-eosin and Masson. The expression levels of hydroxyproline, interleukin (IL)-33, IL-37, tissue plasminogen activator, and plasminogen activator inhibitor-1 were determined by enzyme-linked immunosorbent assay. Results: Mice in the model group were poor in spirit, less active, slow in response, showed reduced food/water intake, body temperature, and body weight, increased respiratory rate, and their tongue color had changed from light red to dark red. However, treatment with FBR-2 significantly improved these symptoms. Extensive inflammatory cell infiltration and collagen fiber deposition were observed in the lung tissues of the model group. Compared with the blank group, the levels of hydroxyproline, IL-33, and plasminogen activator inhibitor-1 in the model group significantly increased (all P

Abstract Background Malunion and nonunion of vertically displaced pelvic fractures result in lower limb length discrepancies, claudication, and pain. There have been few previous reports of this type of corrective surgery for these old pelvic fractures. We present a surgical technique of sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion and nonunion of vertically displaced pelvic fractures and report on its short-term clinical results. Methods We retrospectively reviewed nine patients (five males and four females) with malunion or nonunion of vertically displaced pelvic fractures treated with sacral osteotomy and triangular osteosynthesis from April 2015 to January 2020. The age ranged from 14 to 45 years (average, 30.7 years). The time from injury to deformity correction surgery ranged from 3 months to 5 years (average, 12.8 months). The vertical displacement of a unilateral hemipelvis was 3.0–4.5 cm (average, 3.80 cm). According to AO/OTA classification at the initial fracture, there are eight cases in type C1.3 and one case in type C3.3. Sacral osteotomy and triangular osteosynthesis were used in all nine patients. The degree of unilateral hemipelvic reduction was assessed postoperatively based on measurements from the anteroposterior (AP) X-ray. Majeed score and pain visual analog scale (VAS) were used to assess the therapeutic effect of the patients during follow-up. Results In all nine patients, postoperative AP X-ray showed correction displacement of 1.7–3.9 cm (average, 3.20 cm). All the patients were followed up for 6–36 months (average, 12.7 months). At the last follow-up, the Majeed score of pelvic fracture increased from an average of 53.9 points (30–84 points) preoperatively to 87.0 points (72–94 points), and the VAS score for pain decreased from an average of 6.0 points (4–8 points) preoperatively to 1.2 points (0–3 points). None had complications like infection, implant broken, screw loosening, iatrogenic nerve, and blood vessel injury. Conclusion Sacral osteotomy combined with triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fractures can correct significantly vertical displacement of a unilateral pelvis, prolong limb length, and reconstruct the stability of a pelvic ring, achieving good clinical results.

In this work, the FVM method is employed to simulate blood flow behavior within stenosis arteries based on the non-Newtonian Sisko model by using UDF in Fluent. Stenosis is simulated in cone geometry, and influences of different angles of stenosis with different artery radii are studied on the Nusselt number and temperature of blood flow. It is observed that with increasing angles of stenosis and reducing internal radius, the artery is narrowed, which results in enhancement of Nusselt number of blood flow. Thus, the temperature of blood flow is reduced. Also, applying heat fluxes of q“ = 400 W/m2, q” = 800 W/m2, and q“ = 1000 W/m2 prepare temperature enhancement as much as 0.44 K, 0.89 K, and 1.15 K respectively which are important from a medical viewpoint. The maximum temperature is reported as much as 38.2 °C by applying heat flux of q” = 1000 W/m2, which is noticeable for the human body healthy, especially for the function of enzymes and other proteins of the body. Also, with increasing angles of stenosis and reducing internal radius, the artery is tightened and velocity of blood fluid is enhanced which affects blood circulation between tissues and the oxygenation process, temperature variation, and heat transfer alteration of blood flow within the human body. In reality, circulation of blood transfers heat between tissues, and the dimensions of the blood vessels are various, whenever more blood is needed in some vessels of the body due to more activity, these blood vessels expand to supply the required blood while other vessels tight to compensate it. Therefore, present mechanical research is applicable for medical science especially in surgical widening of a blocked or narrowed blood vessel.

At present, the traditional machine learning diagnosis method has some problems, such as the imbalance of various fault types and the great difference of recognition effect between different fault types. In order to solve the problem of low accuracy of traditional machine learning diagnosis methods, a multilevel fault diagnosis model of transformer based on hierarchical classification, generalized learning and ensemble learning is established. According to the imbalanced degree of each category sample, the method established the corresponding classifier, and carried on the diagnosis step by step. At the first level, the broad learning system was selected to extract three generalized feature labels—normal, discharge and overheat, which were fused with the original parameter input to guide the nine more detailed state types. In the second-level classifier, EasyEnsemble learning method is used to generate multiple data-balanced training subsets through under-sampling, fully balancing the fault information of most classes and a few classes, and then synthesized the final classifier through parallel training sub-classifiers, avoiding the problem of missing data information due to under-sampling. Experimental results show that, compared with the traditional diagnosis methods, the proposed method improved the generalization characteristics of a few types of faults, improved the overall accuracy rate, and had a more accurate and balanced fault diagnosis effect of power transformer.

The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USCEXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USCEXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USCEXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USCEXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USCEXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis.

Hydrogen gas will be an essential energy carrier for global energy systems in the future. However, non-renewable sources account for 96% of the production. Food wastes have high hydrogen generation potential, which can positively influence global production and reduce greenhouse gas (GHG) emissions. The study evaluates the potential of food waste hydrogen-based power generation through biogas steam reforming and its environmental and economic impact in major Ghanaian cities. The results highlight that the annual hydrogen generation in Kumasi had the highest share of 40.73 kt, followed by Accra with 31.62 kt, while the least potential was in Tamale (3.41 kt). About 2073.38 kt was generated in all the major cities. Hydrogen output is predicted to increase from 54.61 kt in 2007 to 119.80 kt by 2030. Kumasi produced 977.54 kt of hydrogen throughout the 24-year period, followed by Accra with 759.76 kt, Secondi-Takoradi with 255.23 kt, and Tamale with 81.85 kt. According to the current study, Kumasi had the largest percentage contribution of hydrogen (47.15%), followed by Accra (36.60%), Secondi-Takoradi (12.31%), and Tamale (3.95%). The annual power generation potential in Kumasi and Accra was 73.24 GWh and 56.85 GWh. Kumasi and Accra could offset 8.19% and 6.36% of Ghana's electricity consumption. The total electricity potential of 3728.35 GWh could displace 17.37% of Ghana's power consumption. This electricity generated had a fossil diesel displacement capacity of 1125.90 ML and could reduce GHG emissions by 3060.20 kt CO2 eq. Based on the findings, the total GHG savings could offset 8.13% of Ghana's carbon emissions. The cost of power generation from hydrogen is $ 0.074/kWh with an annual positive net present value of $ 658.80 million and a benefit-to-cost ratio of 3.43. The study lays the foundation and opens policy windows for sustainable hydrogen power generation in Ghana and other African countries.

Abstract Whether antibiotics should be included remains greatly debated in Masquelet technique. This study intended to determine the effect of polymethyl methacrylate (PMMA) spacer loaded with different vancomycin concentrations on bone defect repair. Hollow cylindrical spacers consisting of PMMA and varying vancomycin concentrations (0, 1, 2, 4, 6, 8, and 10 g) were prepared. Critical bone defects of rabbits were created at the radial shaft, and spacers were implanted and subsequently intramedullary fixed with retrograde Kirschner’s wires (n = 4 for each vancomycin concentration). After 4 weeks, the induced membranes were opened and cancellous allografts were implanted into the defects. Eight weeks post-operatively, the results of X-ray, histology, and micro-CT revealed that some cortical bone was formed to bridge the gap and the bone marrow cavity was formed over time. Quantitatively, there was more new bone formation in the groups with a relatively lower vancomycin concentration (1–4 g) compared with that in the groups with a higher vancomycin concentration (6–10 g). Our findings suggested that PMMA spacers loaded with relatively lower vancomycin concentrations (1–4 g) did not interfere with new bone formation, whereas spacers loaded with relatively higher vancomycin concentrations (6–10 g) had negative effects on bone formation.

Abstract Papillary thyroidal carcinoma (PTC) is a common endocrine cancer that plagues people across the world. The potential roles of long non-coding RNAs (lncRNAs) in PTC have gained increasing attention. In this study, we aimed to explore whether lncRNA ROR affects the progression of PTC, with the involvement of tescalcin (TESC)/aldehyde dehydrogenase isoform 1A1 (ALDH1A1)/βIII-tubulin (TUBB3)/tensin homolog (PTEN) axis. PTC tumor and adjacent tissues were obtained, followed by measurement of lncRNA ROR and TESC, ALDH1A1, and TUBB3 expression. Interactions among lncRNA ROR, TESC, ALDH1A1, TUBB3, and PTEN were evaluated by ChIP assay, RT-qPCR, or western blot analysis. After ectopic expression and depletion experiments in PTC cells, MTT and colony formation assay, Transwell assay, and flow cytometry were performed to detect cell viability and colony formation, cell migration and invasion, and apoptosis, respectively. In addition, xenograft in nude mice was performed to test the effects of lncRNA ROR and PTEN on tumor growth in PTC in vivo. LncRNA ROR, TESC, ALDH1A1, and TUBB3 were highly expressed in PTC tissues and cells. Overexpression of lncRNA ROR activated TESC by inhibiting the G9a recruitment on the promoter of TESC and histone H3-lysine 9me methylation. Moreover, TESC upregulated ALDH1A1 expression to increase TUBB3 expression, which then reduced PTEN expression. Overexpression of lncRNA ROR, TESC, ALDH1A1 or TUBB3 and silencing of PTEN promoted PTC cell viability, colony formation, migration, and invasion while suppressing apoptosis. Moreover, overexpression of lncRNA ROR increased tumor growth by inhibiting PTEN in vivo. Taken together, the current study demonstrated that lncRNA ROR mediated TESC/ALDH1A1/TUBB3/PTEN axis, thereby facilitating the development of PTC.

With the arrival of the low carbon era, enterprises, as the main body of the market economy, must take the road of low carbon operation whether to fulfill their social responsibilities or to seek enterprise development. However, Chinese enterprises started late to understand the low-carbon economy. So far, except for a few state-owned enterprises, some leading private enterprises and foreign-funded enterprises, they have made remarkable achievements in low-carbon emission reduction. Most enterprises in China have not realized the importance of low carbon emission reduction. In order to step out of the “high carbon” era and coordinate economic development and environmental protection, China must solve the problem of low-carbon transformation of small and medium-sized manufacturing enterprises. How to measure the degree of low carbon transformation, and how the government objectively evaluates the degree of low carbon economic development of enterprises, with a view to formulating corresponding standard incentives and punishment measures for them. It is urgent to establish a sound, reasonable and feasible low carbon operation management indicator system, and comprehensively evaluate the information related to low carbon operation of SMEs through reasonable selection of indicators. According to the connotation of low-carbon enterprises, the economic benefits of enterprises are closely combined with environmental benefits. A set of low carbon operation performance evaluation index system including economy, technology and environment has been constructed. The AHP index weight is calculated by establishing the AHP model and the Data Envelopment Analysis (DEA) index weight is calculated by establishing the DEA model. On this basis, the grey relational evaluation model based on AHP-DEA is established. Then the paper evaluates the performance of representative enterprises’ low carbon operation. Propose corresponding improvement suggestions for the problems reflected in the low carbon operation performance ranking of enterprises and the scoring of various indicators. The research results show that the algorithm has high efficiency and the accuracy of model evaluation is 95.51%. To a certain extent, this study makes up for the research results of the impact of digital transformation on corporate strategic performance, and also provides ideas for the research of corporate financial performance evaluation.

Circular RNA circZNF652 promotes LPS-induced inflammation, contributing to the development of osteoarthritis (OA), indicating the potential involvement of circZNF652 in OA. This study was carried to explore the involvement of circZNF652 in OA. RT-qPCR was performed to analyse the expression of circZNF652 and PTEN mRNA in synovial fluid samples from 60 OA patients and 60 healthy controls. Correlations between circZNF652 and PTEN mRNA were analysed by Pearson’s correlation coefficient. Overexpression and siRNA silencing of circZNF652 were achieved in chondrocytes, followed by performing RT-qPCR and Western blot to analyse the expression of PTEN. The role of circZNF652 and PTEN in regulating the apoptosis of chondrocytes induced by LPS was analysed by cell apoptosis assay. We found that circZNF652 was overexpressed in OA and positively correlated with PTEN, MMP13, and NF-KB mRNA. In chondrocytes, circZNF652 overexpression increased the expression of PTEN, MMP13, and NF-KB; circZNF652 siRNA silencing decreased the expression of PTEN, MMP13, and NF-KB. Moreover, circZNF652 and PTEN positively regulated the apoptosis of chondrocytes induced by LPS. PTEN overexpression reversed the inhibitory effects of circZNF652 siRNA silencing on cell apoptosis. Therefore, circZNF652 is overexpressed in OA and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN.

Abstract Introduction: Overexpressed inflammatory cytokines are the main factors causing rheumatoid arthritis (RA) tissue damage and pathological deterioration, and lncRNAs has found to beinvolved in some autoinflammatory diseases. Methods: We designed this study to investigate the effect of lncRNA linc00152 on rheumatoid arthritis inflammation and explore its molecular mechanism.Result: We found that linc00152 was not only up‐regulated in rheumatoid arthritis fibroblast‐like synoviocytes (RAFLS), but also stimulated by TNF‐α/IL‐1β in adose‐ and time‐dependent manner in RAFLS and this expression depends on the NF‐κB signaling pathway. Conversely, linc00152 promoted TNF‐α/IL‐1β expression in RAFLS induced by TNF‐α/IL‐1β. In addition, we found that linc00152 promoted TAK1 expression by targeting inhibition of miR‐103a and activated TAK1‐mediated NF‐κB pathway. NF‐kB indirectly promotes linc00152 expression by promoting the transcription activity of YY1, and YY1 directly promotes linc00152 expression by binding the promoter of linc00152. Conclusion: Our data suggested that the linc00152/NF‐κB feedback loop promotes RAFLS inflammation via regulating miR‐103a/TAK1 axis and YY1 expression. Thus, linc00152 acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.

A coordinate transformation theory for the acoustic cloak design based on pentamode material was proposed by Norris in 2008. This theory avoids the problem of infinite density at the inner boundary of the inertial cloak, but the structural design of the pentamode material was difficult to be achieved. In order to solve this manufacturing problem, a design scheme of a low scattering cloak with only a few layers of polyurethane materials was proposed in this study. First, the material parameter distribution of the acoustic cloak was obtained based on the coordinate transformation theory. On this basis, the material parameter distribution in the two-dimensional annular acoustic cloak was derived by using linear mapping. Through simulation comparison between the uncovered acoustic cloak and covered acoustic cloak, the equivalent scattering characteristics of obstacles covered with the acoustic cloak were significantly reduced, which shows that anisotropic concealed materials have obvious advantages in acoustic control. When the thickness was given and the frequency was fixed, the sound pressure field of the cloak was simulated under the condition of uniform stratification. With the increase in the number of layers, the stealth effect was better, and the complexity of the preparation of metamaterials was increased. In order to obtain the cloak structure with a simple structure and good stealth performance, the BP neural network genetic algorithm and sound field finite element modeling were used. The minimum scattering area was taken as the optimization goal, and we tried to find the design scheme of a low scattering cloak with only a few layers of polyurethane materials. The optimization results show that when the target frequency is 2 KHz and the number of cloak layers is five, the optimized scattering area is 73% less than that of the uniformly layered structure. This shows that anisotropic stealth materials have obvious advantages in sound control. This study can guide the cell configuration design of polyurethane materials in different positions and greatly simplify the complexity of the manufacturing process of stealth materials.

Poria cocos is a widely used ingredient in traditional Chinese medicine and dietary supplement. In this study, the effects of the ethanol extract of P. cocos on cell proliferation in Neuro-2a neuroblastoma cells and its possible mechanism of action are investigated. The extract inhibited the growth of Neuro-2a cells in a dose-dependent manner with an IC50 value of 34.6 μg/mL. To further elucidate the mechanism by which the extract acts, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed. Transcriptome analysis revealed that the cell cycle as the potential primary target pathway of the extract in Neuro-2a cells. Flow cytometry analysis confirmed that the extract induced cell cycle arrest at G1 phase. Furthermore, the extract also induced apoptosis in Neuro-2a cells. Notably, it was found that Neuro-2a cells exhibited morphological features of differentiation when treated with the extract. This study suggests that P. cocos may be a potential candidate therapeutic agent in combating neuroblastoma.

As an important factor related to the interests of enterprises, the attitude and behavior of employees are related to the company’s survival and the realization of business objectives. However, in recent years, with the rapid development of emerging industries and industry changes, the turnover rate of employees in the whole enterprise has been greatly improved. Frequent turnover of personnel will have a great impact on the stability of the company, the competitiveness of the enterprise, and the operating cost. Employee loyalty and corporate culture satisfaction assessment is the core of sustainable corporate development, but most of the traditional analysis studies are based on the performance approach, using employee overtime, employee achievement, and company effectiveness as data sources, the former performance data is only a side view of the company’s situation, the latter as the data source of this study is a one-sided and involute form, and the data is not stable. Therefore, this paper proposes an analysis of employee loyalty and corporate culture satisfaction assessment based on sentiment analysis, using association rules and sentiment lexicons from anonymous employee evaluations to analyze the actual data.

Glioma is a common primary aggressive tumor with limited clinical treatment. Recently, growing research suggests that gut microbiota is involved in tumor progression, and several probiotics can inhibit tumor growth. However, evidence for the effect of probiotics on glioma is lacking. Here, we found that Bifidobacterium (B.) lactis combined with Lactobacillus (L.) plantarum reduced tumor volume, prolonged survival time and repaired the intestinal barrier damage in an orthotopic mouse model of glioma. Experiments demonstrated that B. lactis combined with L. plantarum suppressed the PI3K/AKT pathway and down-regulated the expression of Ki-67 and N-cadherin. The glioma-inhibitory effect of probiotic combination is also related to the modulation of gut microbiota composition, which is characterized by an increase in relative abundance of Lactobacillus and a decrease in some potential pathogenic bacteria. Additionally, probiotic combination altered fecal metabolites represented by fatty acyls and organic oxygen compounds. Together, our results prove that B. lactis combined with L. plantarum can inhibit glioma growth by suppressing PI3K/AKT pathway and regulating gut microbiota composition and metabolites in mice, thus suggesting the potential benefits of B. lactis and L. plantarum against glioma.

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known “writers”, mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.

Immunochromatographic assay (ICA) plays an important role in in vitro diagnostics because of its simpleness, convenience, fastness, sensitivity, accuracy, and low cost. The employment of magnetic nanoparticles (MNPs), possessing both excellent optical properties and magnetic separation functions, can effectively promote the performances of ICA. In this study, an ICA based on MNPs (MNP–ICA) has been successfully developed for the sensitive detection of carcinoembryonic antigen (CEA). The magnetic probes were prepared by covalently conjugating carboxylated MNPs with the specific monoclonal antibody against CEA, which were not only employed to enrich and extract CEA from serum samples under an external magnetic field but also used as a signal output with its inherent optical property. Under the optimal parameters, the limit of detection (LOD) for qualitative detection with naked eyes was 1.0 ng/mL, and the quantitative detection could be realized with the help of a portable optical reader, indicating that the ratio of optical signal intensity correlated well with CEA concentration ranging from 1.0 ng/mL to 64.0 ng/mL (R2 = 0.9997). Additionally, method comparison demonstrated that the magnetic probes were beneficial for sensitivity improvement due to the matrix effect reduction after magnetic separation, and the MNP–ICA is eight times higher sensitive than ICA based on colloidal gold nanoparticles. The developed MNP–ICA will provide sensitive, convenient, and efficient technical support for biomarkers rapid screening in cancer diagnosis and prognosis.

Returning straw to the field is the most significant straw utilization technique for China’s green development. It can provide nutrients for crop growth and improve soil organic matter content. However, there are no standard parameters for measuring the nutrient content of straw directly returned to the field. In addition, the nutrient content of straw in the field is disregarded and the least researched. Therefore, to address these issues, the current research examines the main nutrient composition of straw returned directly to fields and the potential substitution of straw for chemical fertilizers. This study used the latest data on the crop straw-to-grain ratio and straw’s direct return to the field from the Database of Agricultural Crops Straws Resources in China (DACSRC) as the basis for a detailed estimation of the amount of crop straw nutrient resources and straw’s direct return to the field. The straw nutrient resources were measured based on straw yield and the nitrogen (N), phosphorous (P2O5), and potassium (K2O) contents. The results reveal that the maximum amount of straw returned directly to the fields in China was 517 teragram (Tg), while 128 Tg (25%) of the total was not collected but left on the field. The North China region had an enormous amount of direct straw return at 176 Tg (34%), while South China had the least amount at 26 Tg (5%). The amounts of seasonally available N, P2O5, and K2O from straw directly returned to fields are 2 Tg, 1 Tg, and 7 Tg, respectively. In addition, the amount of available straw nutrient resources returned to the field per hectare (ha) was 78 kg. The quantity of straw-originating seasonally available nutrients corresponds to 23% of the chemical fertilizers applied, which can substitute 10% N, 9% P2O5, and 58% K2O. The study provides critical insights on effective ways to improve straw fertilization through an increased rate of straw returned directly to fields and releasing seasonal nutrients.

Abstract Polyvinyl alcohol (PVA) hydrogel has gained interest in cartilage repair because of its highly swollen, porosity, and viscoelastic properties. However, PVA has some deficiencies, such as its poor biocompatibility and microstructure. This research aimed to design novel hydroxyapatite (HA)-collagen (COL)-PVA hydrogels. COL was added to improve cell biocompatibility, and the microstructure of the hydrogels was controlled by fused deposition modeling (FDM). The feasibility of the COL-HA-PVA hydrogels in cartilage repair was evaluated by in vitro and in vivo experiments. The scanning electron microscopy results showed that the hybrid hydrogels had interconnected macropore structures that contained a COL reticular scaffold. The diameter of the macropore was 1.08–1.85 mm, which corresponds to the diameter of the denatured PVA column. The chondrocytes were then seeded in hydrogels to assess the cell viability and formation of the cartilage matrix. The in vitro results revealed excellent cellular biocompatibility. Osteochondral defects (8 mm in diameter and 8 mm in depth) were created in the femoral trochlear of goats, and the defects were implanted with cell-seeded hydrogels, cell-free hydrogels, or a blank control. The in vivo results showed that the COL-HA-PVA hydrogels effectively repaired cartilage defects, especially the conditions inoculated with chondrocyte in advance. This research suggests that the COL-HA-PVA hydrogels have promising application in cartilage repair.

Abstract Background This study aimed to explore the clinical efficacy of treating a first metacarpal base fracture by closed reduction and percutaneous parallel K-wire interlocking fixation between the first and second metacarpals. Methods Twenty patients treated by the abovementioned modified technique (modified technique group) and ten patients treated by the traditional percutaneous K-wire fixation technique (traditional technique group) from October 2015 to November 2019 at our institution were retrospectively reviewed. The patients’ average age was 38 years (range, 16–61 years). The mean follow-up period was 13 months (range, 10–18 months). At the final follow-up, the functional recovery of the injured hand was assessed and compared between the modified and traditional technique groups. In addition, the functional recovery of the injured hand was compared with that of the uninjured hand within the modified technique group. Results All patients recovered well, with no cases of infection or nonunion. Compared with the traditional technique group, the modified technique group had a shorter operative time, lower postoperative visual analogue scale pain score, better effective range of motion score of the first carpometacarpal joint (Kapandji score), and had almost no need for auxiliary plaster fixation, enabling functional exercise to be started earlier. Within the modified technique group, the mean hand grip strength, pinch strength, and Kapandji score on the injured side did not significantly differ to the values on the uninjured side in both the extra-articular and intra-articular fracture subgroups. While the abduction and flexion–extension arcs of the thumb on the injured hand were significantly smaller than those on the uninjured hand in both the extra-articular and intra-articular fracture subgroups, the patients felt clinically well with respect to daily activities and strength. Conclusion The percutaneous parallel K-wire and interlocking fixation technique is simple, effective, and economical for first metacarpal base fractures.

Periprosthetic osteolysis is a major long-term complication of total joint replacement. A series of biological reactions caused by the interaction of wear particles at the prosthesis bone interface and surrounding bone tissue cells after artificial joint replacement are vital reasons for aseptic loosening. Disorder of bone metabolism and aseptic inflammation induced by wear particles are involved in the occurrence and development of aseptic loosening of the prosthesis. Promoting osteogenesis and angiogenesis and mediating osteoclasts and inflammation may be beneficial in preventing the aseptic loosening of the prosthesis. Current research about the prevention and treatment of aseptic loosening of the prosthesis focuses on drug, gene, and stem cell therapy and has not yet achieved satisfactory clinical efficacy or has not been used in clinical practice. Exosomes are a kind of typical extracellular vehicle. In recent years, stem cell exosomes (Exos) have been widely used to regulate bone metabolism, block inflammation, and have broad application prospects in tissue repair and cell therapy.

Growth promotion and stress tolerance induced by endophytes have been observed in various plants, but their effects on mulberry regularly suffering flood in the hydro-fluctuation belt are less understood. In the present study, endophytic Klebsiella aerogenes HGG15 was screened out from 28 plant growth promotion (PGP) bacteria as having superior PGP traits in vitro and in planta as well as biosafety for silkworms. K. aerogenes HGG15 could actively colonize into roots of mulberry and subsequently transferred to stems and leaves. The 16S ribosomal RNA (V3–V4 variable regions) amplicon sequencing revealed that exogenous application of K. aerogenes HGG15 altered the bacterial community structures of mulberry roots and stems. Moreover, the genus of Klebsiella was particularly enriched in inoculated mulberry roots and was positively correlated with mulberry development and soil potassium content. Untargeted metabolic profiles uncovered 201 differentially abundant metabolites (DEMs) between inoculated and control mulberry, with lipids and organo-heterocyclic compounds being particularly abundant DEMs. In addition, a high abundance of abiotic stress response factors and promotion growth stimulators such as glycerolipid, sphingolipid, indole, pyridine, and coumarin were observed in inoculated mulberry. Collectively, the knowledge gained from this study sheds light on potential strategies to enhance mulberry growth in hydro-fluctuation belt, and microbiome and metabolite analyses provide new insights into the growth promotion mechanisms used by plant-associated bacteria.

Safety has always been an important issue affecting the development of traditional Chinese medicine industry, especially for toxic medicinal materials, the establishment of risk prevention and control measures for toxic herbs is of great significance to improving the use of traditional Chinese medicine in clinical. Fuzi is a kind of traditional Chinese medicine and its toxicity has become the most important obstacle of limit in clinical using. In this paper, network pharmacology and molecular docking technology were used to analyze the main toxic components of Fuzi, the key targets and the mechanism of neurotoxicity. We carried out CCK-8 and WB assays, and detected LDH release and SDH activity. It was verified that aconitine caused neurotoxicity through a variety of pathways, including MAPK signaling pathway, pathways related to Akt protein, destruction of cell membrane integrity, damage of mitochondrial function affecting energy metabolism and apoptosis. What’s more, this study confirmed that aconitine could produce neurotoxicity by promoting apoptosis of hippocampus neuron and decreasing its quantity through Nissl Staining and TUNEL assay. This paper found and confirmed multiple targets and various pathways causing neurotoxicity of Fuzi, in order to provide reference for clinical application and related research.

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.

Abstract Over 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming “herd-immunity” through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.

Abstract Background Due to large genetic and phenotypic heterogeneity, the conventional workup for Charcot-Marie-Tooth (CMT) diagnosis is often underpowered, leading to diagnostic delay or even lack of diagnosis. In the present study, we explored how bioinformatics analysis on whole-exome sequencing (WES) data can be used to diagnose patients with CMT disease efficiently. Case presentation The proband is a 29-year-old female presented with a severe amyotrophy and distal skeletal deformity that plagued her family for over 20 years since she was 5-year-old. No other aberrant symptoms were detected in her speaking, hearing, vision, and intelligence. Similar symptoms manifested in her younger brother, while her parents and her older brother showed normal. To uncover the genetic causes of this disease, we performed exome sequencing for the proband and her parents. Subsequent bioinformatics analysis on the KGGSeq platform and further Sanger sequencing identified a novel homozygous GDAP1 nonsense mutation (c.218C > G, p.Ser73*) that responsible for the family. This genetic finding then led to a quick diagnosis of CMT type 4A (CMT4A), confirmed by nerve conduction velocity and electromyography examination of the patients. Conclusions The patients with severe muscle atrophy and distal skeletal deformity were caused by a novel homozygous nonsense mutation in GDAP1 (c.218C > G, p.Ser73*), and were diagnosed as CMT4A finally. This study expanded the mutation spectrum of CMT disease and demonstrated how affordable WES could be effectively employed for the clinical diagnosis of unexplained phenotypes.

Abstract Background To analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP). Methods A total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images. Results In mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P

Plant growth-promoting rhizobacteria have been shown to play important roles in maintaining host fitness under periods of abiotic stress, and yet their effect on mulberry trees which regularly suffer drought after flooding in the hydro-fluctuation belt of the Three Gorges Reservoir Region in China remains largely uncharacterized. In the present study, 74 bacterial isolates were obtained from the rhizosphere soil of mulberry after drought stress, including 12 phosphate-solubilizing and 10 indole-3-acetic-acid-producing isolates. Bacillus megaterium HGS7 was selected for further study due to the abundance of traits that might benefit plants. Genomic analysis revealed that strain HGS7 possessed multiple genes that contributed to plant growth promotion, stress tolerance enhancement, and antimicrobial compound production. B. megaterium HGS7 consistently exhibited antagonistic activity against phytopathogens and strong tolerance to abiotic stress in vitro. Moreover, this strain stimulated mulberry seed germination and seedling growth. It may also induce the production of proline and antioxidant enzymes in mulberry trees to enhance drought tolerance and accelerate growth recovery after drought stress. The knowledge of the interactions between rhizobacteria HGS7 and its host plant might provide a potential strategy to enhance the drought tolerance of mulberry trees in a hydro-fluctuation belt.

Abstract The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2‐S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT‐EZH2 axis is important in TGFβ‐induced epithelial‐mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2‐S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2‐S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2‐S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.

Frogs play an important role in ecological systems, while frog species across the globe are threatened and declining. Therefore, it is valuable to estimate the frog population based on an intelligent computer system. Due to the success of deep learning (DL) in various pattern recognition tasks, previous studies have used DL-based methods for frog call analysis. However, the performance of DL-based systems is highly affected by their input (feature representation). In this study, we develop a frog calling activity detection system for continuous field recordings using a light convolutional neural network (CNN) with multi-view spectrograms. To be specific, a sliding window is first applied to continuous recordings for obtaining audio segments with a fixed duration. Then, the background noise is filtered out. Next, a multi-view spectrogram is used for characterizing those segments, which has more distinctive information than a single-view spectrogram. Finally, a lightweight CNN model is used for the detection of frog calling activity with a twin loss, where different train and test sets are used to validate the model’s robustness. Our experimental results indicate that the highest macro F1-score was 99.6 ± 0.2 and 96.4 ± 2.0 using 2016 and 2017 as the train data respectively, where CNN-GAP is used as the model with multi-view spectrogram as the input.

In this paper, we obtain some results about the existence and multiplicity of weak solutions for a class of damped-like fractional differential system with a parameter $\lambda$. When the nonlinear term is subquadratic only near the origin, we obtain that system has a ground state weak solution $u_\lambda$ if $\lambda$ is in some given interval, and when the nonlinear term is also even near the origin, then for each $\lambda>0$, system has infinitely many weak solutions $\{u_n^\lambda\}$ with $\|u_n^\lambda\|\to 0$ as $n\to \infty$. We mainly use Ekeland's variational principle and a variant of Clark's theorem together with a cut-off technique to prove our results.

The problems of sub-synchronous oscillation and high-frequency oscillation related to inter-harmonics need to be solved in intermittent energy generation systems. The paper proposes a new Phase-Shifted Rotating Pulse Width Modulation (PSR-PWM) technique for specific inter-harmonics control, which can eliminate the specific inter-harmonic that may cause related inter-harmonic oscillations in power system. Based on the time-shift and phase-shift characteristic of signals, the initial phase angle of a characteristic harmonic is linearly modulated to realize the frequency control of moving the spectrum to the desired inter-harmonic spectrum. Therefore, the inverter controlled by the proposed PWM technique behaves as a controlled inter-harmonic voltage source, so as to suppress the specific inter-harmonics in the grid. The analysis of typical simulation cases shows that the maximum frequency offset range for any modulated output voltage characteristic harmonic of the inverter is from -50Hz to 50Hz theoretically. The amplitude of the inter-harmonic voltage combined with its phase angle and frequency can be continuously controlled over a wide frequency range simultaneously, and the suppression effect of other parasitic inter-harmonics is obviously better. Finally, the feasibility and correctness of proposed PSR-PWM techniques are verified by MATLAB simulations and experiments. This paper can be helpful for the study of new energy grid-connected inverters to damp sub-synchronous oscillations and high-frequency oscillation.

MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.

Hmong–Mien (HM) -speaking populations, widely distributed in South China, the north of Thailand, Laos, and Vietnam, have experienced different settlement environments, dietary habits, and pathogenic exposure. However, their specific biological adaptation remained largely uncharacterized, which is important in the population evolutionary genetics and Trans-Omics for regional Precision Medicine. Besides, the origin and genetic diversity of HM people and their phylogenetic relationship with surrounding modern and ancient populations are also unknown. Here, we reported genome-wide SNPs in 52 representative Miao people and combined them with 144 HM people from 13 geographically representative populations to characterize the full genetic admixture and adaptive landscape of HM speakers. We found that obvious genetic substructures existed in geographically different HM populations; one localized in the HM clines, and others possessed affinity with Han Chinese. We also identified one new ancestral lineage specifically existed in HM people, which spatially distributed from Sichuan and Guizhou in the north to Thailand in the south. The sharing patterns of the newly identified homogenous ancestry component combined the estimated admixture times via the decay of linkage disequilibrium and haplotype sharing in GLOBETROTTER suggested that the modern HM-speaking populations originated from Southwest China and migrated southward in the historic period, which is consistent with the reconstructed phenomena of linguistic and archeological documents. Additionally, we identified specific adaptive signatures associated with several important human nervous system biological functions. Our pilot work emphasized the importance of anthropologically informed sampling and deeply genetic structure reconstruction via whole-genome sequencing in the next step in the deep Chinese Population Genomic Diversity Project (CPGDP), especially in the regions with rich ethnolinguistic diversity.

Drought stress often leads to heavy losses in mulberry planting, especially for fruits and leaves. Application of plant growth-promoting fungi (PGPF) endows various plant beneficial traits to overcome adverse environmental conditions, but little is known about the effects on mulberry under drought stress. In the present study, we isolated 64 fungi from well-growing mulberry trees surviving periodical drought stress, and Talaromyces sp. GS1, Pseudeurotium sp. GRs12, Penicillium sp. GR19, and Trichoderma sp. GR21 were screened out due to their strong potential in plant growth promotion. Co-cultivation assay revealed that PGPF stimulated mulberry growth, exhibiting increased biomass and length of stems and roots. Exogenous application of PGPF could alter fungal community structures in the rhizosphere soils, wherein Talaromyces was obviously enhanced after inoculation of Talaromyces sp. GS1, and Peziza was increased in the other treatments. Moreover, PGPF could promote iron and phosphorus absorption of mulberry as well. Additionally, the mixed suspensions of PGPF induced the production of catalase, soluble sugar, and chlorophyll, which in turn enhanced the drought tolerance of mulberry and accelerated their growth recovery after drought. Collectively, these findings might provide new insights into improving mulberry drought tolerance and further boosting mulberry fruit yields by exploiting interactions between hosts and PGPF.

Abstract Background Poly(vinyl alcohol) (PVA) hydrogels have been widely used in synthetic cartilage materials. However, limitations of PVA hydrogels such as poor biomechanics and limited cell ingrowth remain challenges in this field. Methods This work aimed to design novel nano-hydroxyapatite (nano-HA)/poly(vinyl alcohol) (PVA) hydrogels coated with a poly(lactic-co-glycolic acid) (PLGA)/nano-HA/PVA scaffold to counter the limitations of PVA hydrogels. The core, comprising nano-HA/PVA hydrogel, had the primary role of bearing the mechanical load. The peripheral structure, composed of PLGA/nano-HA/PVA, was designed to favor interaction with surrounding cartilage. Results The double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold was successfully prepared using a two-step molding method, and the mechanical properties and biocompatibility were characterized. The mechanical properties of the novel PLGA/HA/PVA scaffold modified HA/PVA hydrogel were similar to those of native cartilage and showed greater sensitivity to compressive stress than to tensile stress. Rabbit chondrocytes were seeded in the composites to assess the biocompatibility and practicability in vitro. The results showed that the peripheral component comprising 30 wt% PLGA/5 wt% HA/15 wt% PVA was most conducive to rabbit chondrocyte adhesion and proliferation. Conclusions The study indicated that the double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold has the potential for cartilage repair.

Background: Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening. Periprosthetic osteolysis is often treated with revision surgery because of the lack of effective therapeutic agents. As key messengers of intercellular interactions, exosomes can be independently used as therapeutic agents to promote tissue repair and regeneration. In this study, we fabricated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that carry exosomes derived from human urine stem cells (USC-Exos) and explored their effects on polyethylene-induced osteolysis.Methods: USCs were identified by multipotent differentiation and flow cytometry analyses. USC-Exos were isolated and identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. PLGA microspheres containing USC-Exos were fabricated to synthesize NPs using the mechanical double-emulsion method. The obtained NPs were characterized in terms of stability, toxicity, exosome release, and cell uptake. Then, these NPs were implanted into the murine air pouch model, and their effects on polyethylene-induced osteolysis were evaluated by microcomputed tomography (micro-CT) and histological analyses.Results: The average NP diameter was ~282 ± 0.4 nm, and the zeta potential was −2.02 ± 0.03 mV. After long-term storage at room temperature and 4°C, the NP solution was stable without significant coaggregation. In vitro release profiles indicated sustained release of exosomes for 12 days. In vivo, injection of NPs into the murine air pouch caused less osteolysis than that of USC-Exos, and NPs significantly reduced bone absorption, as indicated by histology and micro-CT scanning.Conclusion: Our findings suggest that USC-Exo-based PLGA NPs can prevent particulate polyethylene-induced osteolysis and bone loss.

Purpose: To evaluate the long-term retinal microvascular, neural, and choroidal changes in the patients with severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP).Methods: Forty-five eyes of 28 patients with treatment-naive severe NPDR and PDR were included and followed for 12 months after PRP. Microvascular and neural changes in the macular and peripapillary areas were assessed by using optical coherence tomography angiography. Subfoveal choroidal thickness (SFCT) was measured by using optical coherence tomography. A Linear mixed-effects model was used to highlight the differences for the variables after adjusting for sex, age, and axial length.Results: Compared to baseline, there were no statistical differences in the best corrected visual acuity (BCVA), macular and peripapillary vessel density (VD), and SFCT following PRP. Macular thickness significantly increased at 1 and 3–6 months after PRP (p < 0.05), while the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness significantly increased at 1 month postoperatively (p < 0.01). Global loss volume and focal loss volume significantly decreased at the same time point (p < 0.05).Conclusion: The unchanged BCVA, VD, the thickness of RNFL and GCC, and SFCT during the 12-month follow-up period suggest that PRP may prevent the retinal neurovascular and choroidal damage.

A terahertz dual-mode extended interaction oscillator (EIO) driven by a pseudospark-sourced sheet electron beam (SEB) was presented. The major advantages of the newly developed circuit include 1) high-density SEB interacting with the TM11 and TM31 modes, respectively, and 2) high output power of over 1 ​kW ​at the sub-terahertz frequency range. Two different types of 2π modes and their output characteristics were studied, and the circuit was optimized to ensure efficient outputs of two standing-wave modes. The three-dimensional (3D) particle-in-cell (PIC) simulation predicts the maximum output power of 1.3 ​kW with a 3-dB bandwidth of ~0.5 ​GHz ​at 303 ​GHz when operating at the TM11 mode, and 3.18 ​kW, 3-dB bandwidth of ~0.85 ​GHz ​at 364 ​GHz when operating at the TM31 mode.