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The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the “one fungus, one name” principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

Abstract γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in various fields, including food, biomedical and environmental fields. In this study, we screened natto samples for two strains of Bacillus subtilis N3378-2at and N3378-3At that produce γ-PGA. We then identified the γ-PGA synthetase gene cluster (PgsB, PgsC, PgsA, YwtC and PgdS), glutamate racemase RacE, phage-derived γ-PGA hydrolase (PghB and PghC) and exo-γ-glutamyl peptidase (GGT) from the genome of these strains. Based on these γ-PGA-related protein sequences from isolated Bacillus subtilis and 181 B. subtilis obtained from GenBank, we carried out genotyping analysis and classified them into types 1–5. Since we found B. amyloliquefaciens LL3 can produce γ-PGA, we obtained the B. velezensis and B. amyloliquefaciens strains from GenBank and classified them into types 6 and 7 based on LL3. Finally, we constructed evolutionary trees for these protein sequences. This study analyzed the distribution of γ-PGA-related protein sequences in the genomes of B. subtilis, B. velezensis and B. amyloliquefaciens strains, then the evolutionary diversity of these protein sequences was analyzed, which provided novel information for the development and utilization of γ-PGA-producing strains.

BackgroundThe current increasing trend of new cases of occupational noise-induced deafness indicates that the hearing loss of occupational population has not been effectively controlled in China. It is of great significance to study the characteristics of hearing loss among noise-exposed workers and its related factors. ObjectiveTo investigate characteristics and influencing factors of hearing loss among occupational noise-exposed workers in a large machinery maintenance enterprise, and to provide a scientific basis to prevent and control noise-induced hearing loss. MethodsA cross-sectional survey was conducted to investigate male Han occupational noise-exposed workers in a large mechanical maintenance enterprise. We acquired demographic characteristics, occupational exposure history, and individual life behavior characteristics of the workers through questionnaires, collected occupational exposure level data from annual occupational disease hazard factor surveillance reports, obtained pure tone hearing threshold test data through occupational health examinations, and estimated individual noise exposure levels using cumulative noise exposure (CNE). According to the results of pure tone air conduction hearing threshold test, the workers were divided into a hearing loss group and a normal hearing group. The chi-square test was employed to compare the occupational exposure characteristics and individual life behavior characteristics between the two groups. Additionally, the trend chi-square test was utilized to analyze the changing trends of age, length of service, CNE, and hearing loss rate within the two groups. The relationship between high-frequency hearing loss in both ears and its related influencing factors was assessed by a multiple logistic regression model. ResultsThe M (P25, P75) of CNE for the 2531 occupational noise-exposed workers was 97.51 (95.39, 99.96) dB(A)·year. The incidence of hearing anomaly, binaural high-frequency hearing anomaly, random ear high-frequency hearing anomaly, binaural low-frequency hearing anomaly, and random ear low-frequency hearing anomaly were 22.48%, 16.59%, 22.13%, 2.77%, and 3.52%, respectively. High-frequency hearing threshold increase was the main reason for hearing anomaly (98.42%). In comparison to the CNE ≤ 97 dB(A)·year group, the 97 dB(A)·year100 dB(A)·year group experienced a 36.4% and 52.3% increase in the risk of bilateral high-frequency hearing loss, respectively. The smoking group exhibited a 43.5% elevated risk of bilateral high-frequency hearing loss when compared to the non-smoking group. Conversely, the group frequently wearing hearing protection equipment demonstrated a 23.6% lower risk of bilateral high-frequency hearing loss in comparison to the group occasionally wearing protective equipment. The data suggested that CNE＞97 dB(A)·year and smoking might be independent risk factors for bilateral high-frequency hearing loss, and frequently wearing hearing protection equipment might be an important protective factor.ConclusionIncreased CNE and smoking can elevate the risk of high-frequency hearing loss, while personal hearing protection can effectively reduce the risk of hearing loss.

Abstract Objective The aim of this study was to investigate the clinical efficacy of small plate assisted anatomical plate and traditional double plate in the treatment of Rüedi and Allgöwer II - III pilon fracture. Methods and materials The data of 68 patients with pilon fracture admitted to Hospital from June 2017 to June 2020 were retrospectively analyzed. Study group and control group were divided according to different operation methods, with 34 cases in each group. There were 28 cases of Rüedi and Allgöwer II type and 40 cases of Rüedi and Allgöwer III type. Perioperative period data, Ankle joint function score, visual analog scale (VAS) scores and the incidence of incision complications were analyzed between these two groups. Results There were no significant differences in full load time, fracture healing time between these two groups (P > 0.05). The operation time, intraoperative blood loss, length of hospital stay, Ankle joint function score and postoperative incision complication rate in observation group were lower than those in control group (P

In order to extract the line-spectrum features of underwater acoustic targets in complex environments, an auditory convolutional neural network (ACNN) with the ability of frequency component perception, timbre perception and critical information perception is proposed in this paper inspired by the human auditory perception mechanism. This model first uses a gammatone filter bank that mimics the cochlear basilar membrane excitation response to decompose the input time-domain signal into a number of sub-bands, which guides the network to perceive the line-spectrum frequency information of the underwater acoustic target. A sequence of convolution layers is then used to filter out interfering noise and enhance the line-spectrum components of each sub-band by simulating the process of calculating the energy distribution features, after which the improved channel attention module is connected to select line spectra that are more critical for recognition, and in this module, a new global pooling method is proposed and applied in order to better extract the intrinsic properties. Finally, the sub-band information is fused using a combination layer and a single-channel convolution layer to generate a vector with the same dimensions as the input signal at the output layer. A decision module with a Softmax classifier is added behind the auditory neural network and used to recognize the five classes of vessel targets in the ShipsEar dataset, achieving a recognition accuracy of 99.8%, which is improved by 2.7% compared to the last proposed DRACNN method, and there are different degrees of improvement over the other eight compared methods. The visualization results show that the model can significantly suppress the interfering noise intensity and selectively enhance the radiated noise line-spectrum energy of underwater acoustic targets.

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent tumor that poses a significant threat to human health, with 80% of cases being primary HCC. At present, Early diagnosis and predict prognosis of HCC is challenging and the it is characterized by a high degree of invasiveness, both of which negatively impact patient prognosis. Natural killer cells (NK) play an important role in the development, diagnosis and prognosis of malignant tumors. The potential of NK cell-related genes for evaluating the prognosis of patients with hepatocellular carcinoma remains unexplored. This study aims to address this gap by investigating the association between NK cell-related genes and the prognosis of HCC patients, with the goal of developing a reliable model that can provide novel insights into evaluating the immunotherapy response and prognosis of these patients. This work has the potential to significantly advance our understanding of the complex interplay between immune cells and tumors, and may ultimately lead to improved clinical outcomes for HCC patients. Methods For this study, we employed transcriptome expression data from the hepatocellular carcinoma cancer genome map (TCGA-LIHC) to develop a model consisting of NK cell-related genes. To construct the NK cell-related signature (NKRLSig), we utilized a combination of univariate COX regression, Area Under Curve (AUC) LASSO COX regression, and multivariate COX regression. To validate the model, we conducted external validation using the GSE14520 cohort. Results We developed a prognostic model based on 5-NKRLSig (IL18RAP, CHP1, VAMP2, PIC3R1, PRKCD), which divided patients into high- and low-risk groups based on their risk score. The high-risk group was associated with a poor prognosis, and the risk score had good predictive ability across all clinical subgroups. The risk score and stage were found to be independent prognostic indicators for HCC patients when clinical factors were taken into account. We further created a nomogram incorporating the 5-NKRLSig and clinicopathological characteristics, which revealed that patients in the low-risk group had a better prognosis. Moreover, our analysis of immunotherapy and chemotherapy response indicated that patients in the low-risk group were more responsive to immunotherapy. Conclusion The model that we developed not only sheds light on the regulatory mechanism of NK cell-related genes in HCC, but also has the potential to advance our understanding of immunotherapy for HCC. With its strong predictive capacity, our model may prove useful in evaluating the prognosis of patients and guiding clinical decision-making for HCC patients.

Pea shoots is a popular vegetable in certain regions of the world due to their unique taste and abundance of health-promoting phytochemicals. The perishable nature and susceptibility to root rot of pea shoots necessitate a new soilless production system located close to the market. This study compared the growth of pea shoots using various cultivation methods in an LED plant factory. The results showed that early topping (4 days after transplanting, ET) promoted early harvest compared to later topping (20 days after transplanting, LT) and increased the number of harvested shoots by extending the harvest time to 2.8 times, ultimately resulting in a substantial yield improvement. Moreover, the yield of ET with a lower planting density (72 plants m−2, ET-LD) was 8.7% higher than ET with a higher planting density (126 plants m−2, ET-HD). Particularly, the average shoot fresh weight (AFW) under ET-LD exceeded that of ET-HD by 48.9%. It is advisable to consider adopting ET-LD for the cultivation of pea shoots in LED plant factories. Based on ET-LD, the yield, nutritional quality, and light use efficiency of pea shoots were further explored at different stages under three levels of light intensity (50, 100, and 150 μmol m−2·s−1). Contrasted against a light intensity of 50 μmol m−2·s−1, AFW, number of harvested shoots, and total fresh yield under a light intensity of 150 μmol m−2·s−1, increased by 60.2%, 62.8%, and 165.1%, respectively. Meanwhile, AFW, photosynthetic capacity, soluble sugar and vitamin C levels in leaves, as well as light use efficiency and photon yield, initially increased and then decreased with the extension of the planting period. Among these, soluble sugar, light use efficiency, and photon yield started to decrease after reaching the maximum value at 60–70 days after transplanting. In conclusion, a light intensity of 150 μmol m−2·s−1 with a photoperiod of 16 h d−1 using LEDs, combined with early topping within a planting period of 60–70 days, proves to be suitable for the hydroponic production of pea shoots in LED plant factories.

Herbal medicines are widely used for clinical purposes worldwide. These herbs are susceptible to phytopathogenic fungal invasion during the culturing, harvesting, storage, and processing stages. The threat of fungal and mycotoxin contamination requires the evaluation of the health risks associated with these herbal medicines. In this study, we collected 138 samples of 23 commonly used herbs from 20 regions in China, from which we isolated a total of 200 phytopathogenic fungi. Through morphological observation and ITS sequencing, 173 fungal isolates were identified and classified into 24 genera, of which the predominant genera were Fusarium (27.74%) and Alternaria (20.81%), followed by Epicoccum (11.56%), Nigrospora (7.51%), and Trichocladium (6.84%). Quantitative analysis of the abundance of both Fusarium and Alternaria in herbal medicines via RT-qPCR revealed that the most abundant fungi were found on the herb Taraxacum mongolicum, reaching 300,000 copies/μL for Fusarium and 700 copies/μL for Alternaria. The in vitro mycotoxin productivities of the isolated Fusarium and Alternaria strains were evaluated by using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and it was found that the Fusarium species mainly produced the acetyl forms of deoxynivalenol, while Alternaria species mainly produced altertoxins. These findings revealed widely distributed fungal contamination in herbal medicines and thus raise concerns for the sake of the quality and safety of herbal medicines.

ObjectiveThe workers in emerging manufacturing are at decreased risk of traditional occupational diseases, while probably at increased risk of work-related musculoskeletal disorders (WMSDs). This study aimed to investigate the prevalence and risk factors of WMSDs among emerging manufacturing workers in Beijing.MethodsA total of 3,359 valid questionnaires were collected from 10 enterprises in the electronics, pharmaceutical, and motor manufacturing industries. The prevalence of WMSDs was assessed using the Nordic Musculoskeletal Questionnaire. The work posture load was evaluated through a questionnaire.ResultsThe results showed that the highest prevalence of WMSDs was observed in part of the neck (15.0%), followed by the lower back (12.5%), shoulders (11.2%), and upper back (7.1%). Female workers, workers aged older than 35 years, workers with a BMI of ≥28 kg/m2, longer working experience, never exercised had a higher prevalence of WMSDs. Logistic regression analysis showed that female workers, workers aged older than 35 years, with a middle school education and college degree, and workers who never exercised had a higher risk of WMSDs. In addition, workers who sat for long during work, worked hard with upper limbs or hands, worked in uncomfortable postures, and performed repetitive operations were positively related with the increased risk of WMSDs.ConclusionThese findings suggested that WMSDs were prevalent among emerging manufacturing workers in Beijing, China, while efforts should be made to reshape the risk factors associated with WMSDs, such as prolonged sitting, uncomfortable positions, and repetitive operations. Encouraging exercise and promoting ergonomic interventions probably be also benefit to induce the risk of WMSDs.

Abstract Resistance to radiotherapy remains a major unmet clinical obstacle in the treatment of locally advanced rectal cancer. Cancer stem cells (CSCs) are considered to mediate tumor development and radioresistance. However, the role of CSCs in regulating resistance to radiotherapy in colorectal cancer (CRC) remains largely unknown. We established two radioresistant CRC cell lines, HCT116-R and RKO-R, using fractionated irradiation. Analysis using miRNA sequencing and quantitative real-time PCR confirmed lower levels of miR-7-5p in both of the radioresistant cells compared to their parental cells. Subsequently, we validated that miR-7-5p expression was decreased in cancerous tissues from radiotherapy-resistant rectal cancer patients. The Cancer Genome Atlas (TCGA) database analyses revealed that low miR-7-5p expression was significantly correlated with poor prognosis in CRC patients. Overexpression of miR-7-5p led to a rescue of radioresistance and an increase in radiation-induced apoptosis, and attenuated the stem cell-like properties in HCT116-R and RKO-R cells. Conversely, knocking down miR-7-5p in parental HCT116 and RKO cells suppressed the sensitivity to radiation treatment and enhance cancer cell stemness. Stemness-associated transcription factor KLF4 was demonstrated as a target of miR-7-5p. Rescue experiments revealed that miR-7-5p/KLF4 axis could induce radiosensitivity by regulating CSCs in colorectal cancer cells. Furthermore, we used CRC tumor tissues which exhibited resistance to neoadjuvant radiotherapy to establish a patient-derived xenograft (PDX) mouse model. Tail vein injection of magnetic nanoparticles carrying miR-7-5p mimics into the PDX mice significantly inhibited tumor growth with or without irradiation treatment in vivo. Our current studies not only demonstrate an anti-cancer function of miR-7-5p in regulating CSC properties and radiosensitivity in colorectal cancer, but also provide a novel potential strategy for delaying or reverse radiation resistance in preoperative radiotherapy of CRC patients.

The low-frequency line spectrum of the radiated noise signals of hydroacoustic targets contains features describing the intrinsic properties of the target that make the target susceptible to exposure. In order to extract the line spectral features of underwater acoustic targets, a method combining image processing and a deep autoencoder network (DAE) is proposed in this paper to enhance the low-frequency weak line spectrum of underwater targets in an extremely low signal-to-noise ratio environment based on the measured data of large underwater vehicles. A Gauss–Bernoulli restricted Boltzmann machine (G–BRBM) for real-value signal processing was designed and programmed by introducing a greedy algorithm. On this basis, the encoding and decoding mechanism of the DAE network was used to eliminate interference from environmental noise. The weak line spectrum features were effectively enhanced and extracted under an extremely low signal-to-noise ratio of 10–300 Hz, after which the reconstruction results of the line spectrum features were obtained. Data from large underwater vehicles detected by far-field sonar arrays were processed and the results show that the method proposed in this paper was able to adaptively enhance the line spectrum in a data-driven manner. The DAE method was able to achieve more than double the extractable line spectral density in the frequency band of 10–300 Hz. Compared with the traditional feature enhancement extraction method, the DAE method has certain advantages for the extraction of weak line spectra.

Different from centralized and large-scale photovoltaic power station, the sites selection of rail transit photovoltaic power station (RTPPS) concerns more on sustainability rather than profit and there is a lack of selection index system for RTPPS sites selection. Besides that, the decision model cannot deal with the uncertainty, the independence assumption problem and the solving problem of multi-objective programming (MOP) model in scenarios with more goals. The contributions of this paper are as follows: ① a selection index system of RTPPS site selection is established based on RTPPS’s characteristics to provide the scientific decision-making direction; ② the interval-valued Pythagorean fuzzy number (IVPFN) is used to deal with uncertainty in decision information; ③ the fuzzy measure were used to avoid the assumption of independence, which make the decision model is more in line with the reality; ④ the IVPFN-TOPSIS was used to decrease the number of goals, so the MOP model can be solved in scenarios with more goals. The effectiveness of this framework is proved by a China case study. According to the sensitivity analysis and comparative analysis, the decision result calculated by the proposed decision model has good robustness and the site selection framework can better serve the enterprise.

Abstract Background The comparison of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) has not been fully investigated. Here we aimed to explore the applicability of the Willems dental age estimation in an Eastern Chinese population, which may cast light on the field of dental age estimation. Methods A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11–16 years old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value

As a typical pullout foundation, the uplift pile has been widely used in ocean projects or geotechnical engineering, but the accurate prediction of its ultimate pullout capacity has always been a difficulty in engineering design. This study focused on a single pile in rock formation, and constructed a curved uplift failure mechanism in the case that the whole rock mass around the pile was damaged. In this mechanism, the rock mass failure was assumed to comply with the Hoek–Brown failure criterion. Then, the theoretical prediction formulas for the rock failure surface and the ultimate pullout capacity of the pile were derived by using the upper bound theorem. The influence laws of factors such as different rock mass parameters, pile parameters and additional surface load on the pile capacity and failure range were analyzed. Further, the proposed method was validated by comparing with the numerical simulation results. The results show that the ultimate pullout capacity of the pile increases with the increase in the length/diameter ratio, rock empirical parameter A, tensile strength, compressive strength, unit weight and additional surface load, but decreases with the increase in rock empirical parameter B. Empirical parameters A and B are key factors affecting the pile capacity and rock failure range, and should be attached importance to in engineering design. The research work in this study can provide some theoretical reference for the design of the uplift pile in rock formation.

【Objective】The study aims to explore the relationship between the protease-producing capacity of Bacillus and the protease genes carried by the bacteria and analyze the important enzyme genes that affect the protease-producing capacity of Bacillus.【Method】The protease-producing strain was screened by using the selective medium. The protease activity of the strains was determined by the Folin method. The protease genes carried on the chromosomes of the strains were obtained and classified by sequencing the whole genome of 15 strains of Bacillus. The transcription level of protease gene mRNA was measured by the real-time fluorescent quantitative PCR method. Through comparative genomics and Bacterial Genome-Wide Association Analysis (BGWAS), the reasons that affect the ability of bacteria to produce protease were explored.【Result】According to the protease genes carried on the chromosomes of the strains, they could be divided into 7 groups of genotypes (G1-G7). Comparative genomics and BGWAS found that the number of protease genes carried on bacterial chromosomes was directly related to the protease production capacity, and the protease production capacity of strains lacking aprX and aprE was significantly reduced. The difference in the protease production capacity of Bacillus was found to be related to the expression level of aprX by further studying the mRNA level of the gene.【Conclusion】There is a correlation between the protease gene carried on the chromosome of the strain and the protease production capacity of the strain. The important enzyme gene that affects the protease production capacity of Bacillus is aprX.

Abstract Melatonin plays a critical role in promoting the proliferation of osteoblasts and the growth and development of dental papilla cells. However, the effect and mechanism of melatonin on the growth and development of ALCs still need to be explored. CCK8 assay was used for the evaluation of cell numbers. qRT-PCR was used to identify the differentially expressed genes in ALCs after melatonin treatment. The number and morphology of ALCs were investigated by confocal microscopy. Alkaline phosphatase assay and Alizarin red S staining were used for measuring mineralization. Then, we focused on observing the crucial factors of the signaling pathway by RNA-seq and qRT-PCR. Melatonin limited the cell number of ALCs in a dose-dependent manner and promoted the production of actin fibers. A high concentration of melatonin significantly promoted the mRNA levels of enamel matrix proteins and the formation of mineralized nodules. RNA-seq data showed that Wnt signaling pathway may be involved in the differentiation of ALCs under the influence of melatonin. This study suggests that melatonin plays a regulatory role in the cell number, differentiation, and mineralization of the ALCs, and then shows the relationship between the Wnt signaling pathway with the ALCs under melatonin.

Abstract In present work, the abrasive-free jet polishing (AFJP) of bulk single-crystal KDP was first fulfilled, when using a newly-designed low-viscosity microemulsion as the AFJP fluid. The novel AFJP fluid shows a typical water-in-oil structure, in which the water cores uniformly distribute in the BmimPF6 IL, with a particle size of about 20–25 nm. What’s more, the AFJP fluid is a controllable and selective non-abrasive jet fluid that the shape of the removal function is regular and smooth, presenting a similar Gaussian function, meanwhile, the dispersion coefficient of the removal rate is only 1.9%. Finally, the surface quality of the bulk single-crystal KDP is further improved by AFJP, meanwhile, the subsurface damage is first obviously mitigated.

Underwater acoustic target recognition methods based on time-frequency analysis have shortcomings, such as missing information on target characteristics and having a large computation volume, which leads to difficulties in improving the accuracy and immediacy of the target recognition system. In this paper, an underwater acoustic target recognition model based on a deep residual attention convolutional neural network called DRACNN is proposed, whose input is the time-domain signal of the underwater acoustic targets radiated noise. In this model, convolutional blocks with attention to the mechanisms are used to focus on and extract deep features of the target, and residual networks are used to improve the stability of the network training. On the full ShipsEar dataset, the recognition accuracy of the DRACNN model is 97.1%, which is 2.2% higher than the resnet-18 model with an approximately equal number of parameters as this model. With similar recognition accuracies, the DRACNN model parameters are 1/36th and 1/10th of the AResNet model and UTAR-Transformer model, respectively, and the floating-point operations are 1/292nd and 1/46th of the two models, respectively. Finally, the DRACNN model pre-trained on the ShipsEar dataset was migrated to the DeepShip dataset and achieved recognition accuracy of 89.2%. The experimental results illustrate that the DRACNN model has excellent generalization ability and is suitable for a micro-UATR system.

Abstract Background Recently, the dental age estimation method developed by Cameriere has been widely recognized and accepted. Although machine learning (ML) methods can improve the accuracy of dental age estimation, no machine learning research exists on the use of the Cameriere dental age estimation method, making this research innovative and meaningful. Aim The purpose of this research is to use 7 lower left permanent teeth and three models [random forest (RF), support vector machine (SVM), and linear regression (LR)] based on the Cameriere method to predict children's dental age, and compare with the Cameriere age estimation. Subjects and methods This was a retrospective study that collected and analyzed orthopantomograms of 748 children (356 females and 392 males) aged 5–13 years. Data were randomly divided into training and test datasets in an 80–20% proportion for the ML algorithms. The procedure, starting with randomly creating new training and test datasets, was repeated 20 times. 7 permanent developing teeth on the left mandible (except wisdom teeth) were recorded using the Cameriere method. Then, the traditional Cameriere formula and three models (RF, SVM, and LR) were used to estimate the dental age. The age prediction accuracy was measured by five indicators: the coefficient of determination (R2), mean error (ME), root mean square error (RMSE), mean square error (MSE), and mean absolute error (MAE). Results The research showed that the ML models have better accuracy than the traditional Cameriere formula. The ME, MAE, MSE, and RMSE values of the SVM model (0.004, 0.489, 0.392, and 0.625, respectively) and the RF model (− 0.004, 0.495, 0.389, and 0.623, respectively) were lower with the highest accuracy. In contrast, the ME, MAE, MSE and RMSE of the European Cameriere formula were 0.592, 0.846, 0.755, and 0.869, respectively, and those of the Chinese Cameriere formula were 0.748, 0.812, 0.890 and 0.943, respectively. Conclusions Compared to the Cameriere formula, ML methods based on the Cameriere’s maturation stages were more accurate in estimating dental age. These results support the use of ML algorithms instead of the traditional Cameriere formula.

ObjectiveOccupational stress is a critical global public health problem. We aimed to evaluate the prevalence of occupational stress among the workers in the electricity, heat, gas, water production and supply (EHGWPS), manufacturing, and transportation industries in Beijing, China. We explored the demographic differences in occupational stress status among workers in industrial enterprises.MethodsA cross-sectional study was conducted on 13,867 workers. The self-administered New Brief Job Stress Questionnaire was used to evaluate high occupational stress status, which includes four sub-dimensions (job stressors, stress response, social support, job stressors & social support). Multiple regression and logistic regression models were used to estimate the association between high occupational stress and the four occupational stress sub-dimensions with risk factors.ResultsA total of 13,867 workers were included. The prevalence of high occupational stress was 3.3% in the EHGWPS industries, 10.3% in manufacturing, and 5.8% in transportation. The prevalence of high occupational stress was higher than in the other two categories (p < 0.05) in manufacturing industries. Logistic regression analysis showed that male workers with lower educational status, more job experience, and working in manufacturing were vulnerable to high occupational stress. Further analysis of the four occupational stress sub-dimensions showed that male workers, older adult workers, workers with lower educational levels, and longer working time were associated with higher scores in job stressors, stress response, social support, and job stress & social support (all p < 0.05). Moreover, divorced or widowed workers had higher occupational stress scores.ConclusionMale workers with lower educational levels and longer working time may have an increased risk of occupational stress.

Abstract Production of the Fusarium toxin deoxynivalenol (DON) is associated with oxidative stress and has been indicated to be part of an adaptive response to oxidative stress in the important wheat fungus Fusarium graminearum. In this study, we found that the antioxidant methyl gallate (MG) displays inhibitory effects against mycelial growth, conidial formation and germination, and DON biosynthesis in F. graminearum in a dose-dependent manner. Treatment with 0.05% (w/v) MG resulted in an abnormal swollen conidial morphology. The expression of the TRI genes involved in DON biosynthesis was significantly reduced, and the induction of Tri1-GFP green fluorescence signals in the spherical and crescent-shaped toxisomes was abolished in the MG-treated mycelium. RNA-Seq analysis of MG-treated F. graminearum showed that 0.5% (w/v) MG inhibited DON production by possibly altering membrane functions and oxidoreductase activities. Coupled with the observations that MG treatment decreases catalase, POD and SOD activity in F. graminearum. The results of this study indicated that MG displays antifungal activity against DON production by modulating its oxidative response. Taken together, the current study revealed the potential of MG in inhibiting mycotoxins in F. graminearum. Graphical abstract

Abstract Background The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. Methods A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. Results The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0–21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454–0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050–1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. Conclusions Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Background: Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organisation and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship. Methods: Seven hundred and eight participants from the Alzheimer’s Disease Neuroimaging Initiative were studied. Individual-level structural and metabolic covariance scores in higher-level cognitive and hippocampal networks were derived from magnetic resonance imaging and [18F] fluorodeoxyglucose positron emission tomography using seed-based partial least square analyses. The non-linear associations between network scores and memory across cognitive stages in each pathology group were examined using sparse varying coefficient modelling. Results: We showed that the associations of memory with structural and metabolic networks in the hippocampal and default mode regions exhibited pathology-dependent differential trajectories across cognitive stages using sparse varying coefficient modelling. In amyloid pathology group, there was an early influence of hippocampal structural network deterioration on memory impairment in the preclinical stage, and a biphasic influence of the angular gyrus-seeded default mode metabolic network on memory in both preclinical and dementia stages. In non-amyloid pathology groups, in contrast, the trajectory of the hippocampus-memory association was opposite and weaker overall, while no metabolism covariance networks were related to memory. Key findings were replicated in a larger cohort of 1280 participants. Conclusions: Our findings highlight potential windows of early intervention targeting network breakdown at the preclinical AD stage. Funding: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). We also acknowledge the funding support from the Duke NUS/Khoo Bridge Funding Award (KBrFA/2019-0020) and NMRC Open Fund Large Collaborative Grant (OFLCG09May0035), NMRC New Investigator Grant (MOH-CNIG18may-0003) and Yong Loo Lin School of Medicine Research funding.

BackgroundThe predictive role of mismatch repair (MMR) status for survival outcomes and sensitivity in neoadjuvant chemoradiotherapy settings for patients with locally advanced rectal cancer (LARC) has been inconclusive.MethodsA retrospective cohort of patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) was recruited. After adjusting for baseline characteristics, we used propensity score matching to reduce the effect of potential confounding factors on MMR status. The primary analysis was based on overall survival as the more important endpoint.ResultsThis study included 269 patients. Patients with defective MMR (dMMR) were younger (58.5% vs. 60.0%, p=0.0274) and had lower body mass indices (p=0.0091), higher differentiation grades (p=0.0889), and more advanced rectal cancers (clinical T4 or T4b, p=0.0851; M1, p=0.0055) than those with proficient MMR (pMMR). However, propensity score-matched patients with dMMR (p=0.0013) exhibited superior overall survival, even in the M1 subgroup. More importantly, patients with proficient MMR who undergo early pathological downstaging, especially lymph node pathological downstaging, can achieve a prognosis similar to that of patients with dMMR.ConclusionThe clinical significance of this retrospective study mainly includes two points: (1) Data from our study confirmed that LARC patients with dMMR status had better overall survival rates after nCRT, even in the M1 subgroup. (2) Similar survival outcomes were observed in older and female patients with early lymph node pathological downstaging, regardless of dMMR or pMMR.

PurposeEarly childhood developmental delay remains problematic worldwide in terms of weight and the five domains of child development, including gross motor, fine motor, cognition, language, and social domains. Based on the World Health Organization (WHO) guideline and the theoretical domain framework, this study identified five key socioeconomic factors, such as parenting time during hospitalization, parental educational level, medical spending, distance to hospital, and medical insurance coverage, to describe how these five factors are associated with improved outcomes of developmental quotient (DQ) values and the weight of infants in a tertiary hospital.MethodsIn this prospective observational study, clinical and socioeconomic data were collected. Clinical data included the weight and DQ values of infants and other data relevant to the birth of infants. A National Developmental Scale was used to observe infants in five domains and calculate the DQ values of infants. These five domains include gross motor, fine motor, cognition, language, and social domains. Parenting time during hospitalizations was observed by a research nurse. Other socioeconomic factors were reported by parents and verified with system information.ResultsA total of 75 infants' parents were approached, of which 60 were recruited. The age of infants ranged from 75 to 274 days at the first admission. Increments of their weight and DQ values improved from −0.5 to 2.5 kg and from −13 to 63, respectively. More than half of the parents (54.1%) were at the level of minimum secondary education although the results were not statistically significant. However, there was a positive correlation between weight improvement and parenting time during hospitalization (r(58) = 0.258, p < 0.05), medical spending (r(58) = 0.327, p < 0.05), distance to hospital (r(58) = 0.340, p < 0.01), but there was a negative association with medical insurance coverage (r(58) =-0.256, p < 0.05). There was also a significant relationship between the improved DQ value and distance to hospital (r(58)= 0.424, p < 0.01).ConclusionParenting time during hospitalization, medical spending, distance to hospital, and medical insurance coverage are important factors for early childhood developmental delay in relation to possible hospital intervention and improved accessibility to health services for families in rural areas. Therefore, changes in the current medical scheme are needed because a universal medical subsidy among regions will reduce the financial burden of families and provide families with more access to the necessary health services that their children need.

Abstract Stroke leads to both regional brain functional disruptions and network reorganization. However, how brain functional networks reconfigure as task demand increases in stroke patients and whether such reorganization at baseline would facilitate post-stroke motor recovery are largely unknown. To address this gap, brain functional connectivity (FC) were examined at rest and motor tasks in eighteen chronic subcortical stroke patients and eleven age-matched healthy controls. Stroke patients underwent a 2-week intervention using a motor imagery-assisted brain computer interface-based (MI-BCI) training with or without transcranial direct current stimulation (tDCS). Motor recovery was determined by calculating the changes of the upper extremity component of the Fugl–Meyer Assessment (FMA) score between pre- and post-intervention divided by the pre-intervention FMA score. The results suggested that as task demand increased (i.e., from resting to passive unaffected hand gripping and to active affected hand gripping), patients showed greater FC disruptions in cognitive networks including the default and dorsal attention networks. Compared to controls, patients had lower task-related spatial similarity in the somatomotor–subcortical, default–somatomotor, salience/ventral attention–subcortical and subcortical–subcortical connections, suggesting greater inefficiency in motor execution. Importantly, higher baseline network-specific FC strength (e.g., dorsal attention and somatomotor) and more efficient brain network reconfigurations (e.g., somatomotor and subcortical) from rest to active affected hand gripping at baseline were related to better future motor recovery. Our findings underscore the importance of studying functional network reorganization during task-free and task conditions for motor recovery prediction in stroke.

Common fragile sites (CFSs) are specific genomic loci prone to forming gaps or breakages upon replication perturbation, which correlate well with chromosomal rearrangement and copy number variation. CFSs have been actively studied due to their important pathophysiological relevance in different diseases such as cancer and neurological disorders. The genetic locations and sequences of CFSs are crucial to understanding the origin of such unstable sites, which require reliable mapping and characterizing approaches. In this review, we will inspect the evolving techniques for CFSs mapping, especially genome-wide mapping and sequencing of CFSs based on current knowledge of CFSs. We will also revisit the well-established hypotheses on the origin of CFSs fragility, incorporating novel findings from the comprehensive analysis of finely mapped CFSs regarding their locations, sequences, and replication/transcription, etc. This review will present the most up-to-date picture of CFSs and, potentially, a new framework for future research of CFSs.

This study aimed to compare the short-term clinical efficacy between prior and traditional approach of Henle trunk in laparoscopic right hemicolectomy (LRH) for right colon cancer. A total of 161 patients underwent LRH for right colon cancer between June 2018 and December 2020 by the same group of physicians. The prior approach of Henle trunk (priority group) was used in 82 patients and traditional approach in 79 (traditional group). The demographics and clinicopathological characteristics were recorded and retrospectively analyzed. As compared to the traditional group, the mean blood loss reduced significantly [73.84 ± 17.31 mL vs. 83.42 ± 30.16 mL; P = 0.001], the operation time was markedly shorter [151.35 ± 6.75 min vs. 159.13 ± 18.85 min; P = 0.014], and the intraoperative vascular injury rate was significantly lower [6.1% (5/82). vs. 17.7% (14/79); P = 0.022]. There were no significant differences in the postoperative complications, first exhaust time, first defecation time, drainage time, postoperative hospital stay, quality evaluation of surgical specimens and pathological findings between two groups. Our study shows that the priority management of Henle trunk in the LRH for right colon cancer is a safe and feasible procedure with less blood loss, shorter operation time and lower intraoperative vascular injury rate.

AIM: To evaluate the efficacy, predictability and safety of surgical respositioning of in-the-bag intraocular lens dislocated into the vitreous cavity.METHODS: A retrospective case control study was adopted to analyze 8 eyes of 8 patients with spontaneous in-the-bag intraocular lens dislocated into the vitreous cavity. The study was conducted from April 2017 to June 2019. 8 eyes of 8 patients who had undergone standard 23G pars plana vitrectomy and in-the-bag intraocular lens were respositioned by ciliary sutures fixed act as research group.10 eyes of 10 patients with lens dislocated into vitreous cavity, which were performed with phacofragmentation and ciliary sutures fixed during the same period act as the control group. Patients were examined 7, 30 and 60d postoperatively. The examinations included uncorrected visual acuity, best corrected visual acuity, intraocular pressure, corneal astigmatism, the tilt and decentration of the IOL, complacations of surgeries etc.RESULTS: Successful IOL implantations were achieved in all eyes. Visual acuity: At 7, 30, and 60d after surgery, the uncorrected visual acuity of the two groups was both improved compared with before surgery, and the difference was statistically significant(P0.05). There was no difference in uncorrected visual acuity between the two groups, but there was statistically significant difference in uncorrected visual acuity between 7d and 30d, 7d and 60d after operation(P0.05). Intraocular pressure: Intraocular pressure in the two groups was within the normal range(10mmHg-21mmHg)at 7, 30 and 60d after surgery, and there was no statistically significant difference between the groups(P>0.05), while the difference between the groups was not statistically significant. Corneal astigmatism: At 30d after surgery, the corneal astigmatism of the two groups was both increased than before, at 60d after surgery, the corneal astigmatism of the control group was increased than before, and the differences were statistically significant(P

Abstract The Plk1‐interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase DNA bridges in mitosis along with a complex of DNA repair proteins. Previous studies show PICH deficiency‐induced embryonic lethality in mice. However, the function of PICH that is required to suppress embryonic lethality in PICH‐deficient mammals remains to be determined. Previous clinical studies suggest a link between PICH deficiency and the onset of acquired aplastic anemia. Here, using Pich knock‐out (KO) mouse models, the authors provide evidence for a mechanistic link between PICH deficiency and defective hematopoiesis. Fetal livers from Pich‐KO embryos exhibit a significantly elevated number of hematopoietic stem cells (HSCs); however, these HSCs display a higher level of apoptosis and a much‐reduced ability to reconstitute a functional hematopoietic system when transplanted into lethally irradiated recipients. Moreover, these HSCs show an elevated cytoplasmic dsDNA expression and an activation of the cGAS‐STING pathway, resulting in excessive production of type I interferons (IFN). Importantly, deletion of Ifnar1 or cGAS reverses the defective hematopoiesis. The authors conclude that loss of PICH results in defective hematopoiesis via cGAS‐STING‐mediated type I IFN production.

Objectives To evaluate the incidence and risk factors of postoperative pneumonia (POP) in geriatric patients with a hip fracture after surgery, to design a predictive nomogram, and to validate the accuracy of the nomogram. Design Retrospective study. Setting A tertiary hospital affiliated to a medical university. Patients/Participants We retrospectively studied 1285 surgical-treated geriatric patients with a hip fracture from April 2010 to April 2018. Intervention Surgical treatment was performed on the patients of this study. The procedure methods were classified as: total hip arthroplasty, hemiarthroplasty, percutaneous fixation, intramedullary nail fixation, and plate/screw fixation. Main Outcome Measurement The primary interest of end point of this study is the development of POP during the postoperative period. The postoperative period in this study was defined as the time from 24 hours after surgery to discharge. The diagnostic criteria for pneumonia were set according to the guidelines built by the Infectious Diseases Society of America and the American Thoracic Society (Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia, 2005). Potential variables for developing POP were identified using logistic regression analyses initially and were further selected via the method of LASSO. Then the independent risk factors were identified by multivariable regression analyses. A predictive nomogram was built based on the multiple regression model, and the calibration abilities of the nomogram was measured by Harrel C-index, calibration plot and Hosmer–Lemeshow test, respectively. Decision curve analysis was carried out to assess the net benefit due to threshold probability and an on-line questionnaire survey was conducted among the clinicians to assess the applicability of the nomogram coherently. Results Of the 1285 patients, 70 (5.4%) developed POP. COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment were identified as independent risk factors of POP. The nomogram built based on the results showed good accordance between the predicted probabilities and the observed frequency. The decision curve analysis confirmed the clinical utility of the nomogram when the threshold probabilities were between 5% and 65% due to the net benefit, while the results of on-line questionnaire among 200 clinicians showed that 91.5% of the participants had a mental threshold of intervention between 5-50%. Conclusion (1). COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment are independent risk factors for POP. (2). The nomogram built in this study has a good accordance between the predictive risk and the observational incidence. The results of decision curve and questionnaire among clinicians show well applicability of the nomogram.

Objective. This study was to quantitatively synthesize data in randomized controlled trials (RCTs) of laparoscopic resection comparing natural orifice specimen extraction (NOSE) versus conventional laparoscopy (CL) in colorectal cancer. Methods. We identified eligible RCTs by searching seven electronic databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, CQVIP, Wanfang, and Sinomed). Mean differences (MDs) between groups with 95% confidence intervals (CIs) were used for continuous outcomes. Event rate ratios (RRs) were also calculated with their 95% CIs. Results. 1,569 citations were identified from electronic database as of June 2020, and finally, 21 RCTs involving 2,112 patients met the study eligibility criteria and were included. Compared to the CL group, NOSE had longer operation time (MD: 8.14 min, 95% CI: 3.02 to 13.25, and p

Background and purpose — Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods — In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results — Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24–48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation — In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.

Abstract Pyruvate dehydrogenase kinase (PDK) is a mitochondrial enzyme in a variety of eukaryotes, including the plant pathogen Fusarium graminearum. This enzyme can reduce the oxidation of glucose to acetyl-coA by phosphorylation and selectively inhibits the activity of pyruvate dehydrogenase (PDH), which is a kind of pyruvate dehydrogenase complex (PDC). In this study, we investigated the F. graminearum pyruvate dehydrogenase kinase encoded by FgPDK2, which is a homologue of Neurospora crassa PDK2. The disruption of the FgPDK2 gene led to several phenotypic defects including effects on mycelial growth, conidiation, pigmentation, and pathogenicity. The mutants also showed decreased resistance to osmotic stress and cell membrane/wall-damaging agents. The FgPDK2 deletion mutant exhibited reduced virulence. All of these defects were restored by genetic complementation of the mutant with the complete FgPDK2 gene. Overall, the results demonstrated that FgPDK2 is crucial for the growth of F. graminearum and can be exploited as a potential molecular target for novel fungicides to control Fusarium head blight caused by F. graminearum. Graphical abstract

Benefiting from the characteristics of full field scanning, high resolution and high precision, digital fringe projection measurement technology has been widely used in three-dimensional measurement. For the cylinder pose detection, due to the influence of occlusion and noise, the obtained three-dimensional point cloud information is usually incomplete, resulting in the unreliable object parameters after point cloud fitting. In view of the above problems, a cylinder fitting method with incomplete point cloud data based on the cutting plane is proposed. Firstly, the point cloud is processed by bilateral filtering method to reduce the influence of outliers and noise points. Then, according to the principle of forming ellipse on cylinder cutting plane, some equidistant cutting planes are selected. At the same time, in order to reduce the influence of outliers on fitting, the random sampling consistency algorithm is used for ellipse fitting with the points on each cutting plane, that is, the ellipse parameters corresponding to each cutting plane can be obtained. Finally, random sampling consistency algorithm is applied for cylinder axis fitting with the ellipse centers of all the cutting planes, calculating the axis vector of the cylinder. Thus, the parameters of the cylinder detected are obtained. The experimental results of stepped cylinder with diffuse reflection and metal cylinder show the effectiveness and high precision of the proposed method.

Ellipse center extraction is the important basis of camera calibration with circle arrays calibration board, which directly affects the measurement accuracy of machine vision system. Aiming at the problem of high noise sensitivity of the most ellipse center extraction methods, a high robust multi-ellipse center extraction method is proposed. The idea is to transform the problem of multi-ellipse center extraction into the problems of ellipse sub-pixel edge segmentation and edge based ellipse center clustering. Firstly, the flowchart of the proposed method is introduced. Then, the theory of fuzzy quotient space is introduced to establish the dynamic granularity matrix space model, which describes image segmentation problem as the jumping and transformation of the image by hierarchical structure. Finally, an adaptive multi-ellipse sub-pixel edge segmentation method and an optimal ellipse center extraction method are proposed based on the dynamic granularity matrix space model. Experimental results show that the proposed method has higher accuracy, robustness and lower camera calibration error.

Abstract Fusarium mycotoxin contamination of both foods and feeds is an inevitable phenomenon worldwide. Deoxynivalenol, nivalenol, zearalenone, T-2 toxin and fumonisin B1 are the most studied Fusarium mycotoxins. Co-contamination of mycotoxins has also been studied frequently. Fusarium mycotoxins occur frequently in foods at very low concentrations, so there is a need to provide sensitive and reliable methods for their early detection. The present review provides insight on the types, toxicology and occurrence of Fusarium mycotoxins. It further elucidates various detection methods of mycotoxin production from Fusarium strains, with a special focus on chromatographic and immunochemical techniques.

Introduction: Melatonin, an endogenous neurohormone, modulates the biological circadian rhythms of vertebrates. It functions have been reported in previous stomatological studies as anti-inflammation, antioxidant, osseointegration of dental implants and stimulation to dental pulp stem cells differentiation, but its role in ameloblastic differentiation and mineralization has been rarely studied.Objective: To reveal the effects of melatonin on the mineralization of ameloblast lineage cells (ALCs), and to identify the change in gene expression and the potential mechanism based on ribonucleic acid sequencing (RNA-seq) analysis.Method: ALCs were induced in melatonin-conditioned medium. After 7-days culture, Western blot, real-time PCR, alkaline phosphatase (ALP) activity test, RNA-seq were accordingly used to detect the change in molecular level. After 1-month odontogenic induction in melatonin medium, Alizarin Red-S (ARS) staining showed the changes of mineral nodules. Differentially expressed genes (DEGs), enrichment of functions and signaling pathways analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) database were performed. The JNK3 antagonist (JNK3 inhibitor IX, SR3576) and β-arrestin1 (Arrb1) overexpression were applied to confirm the fluctuation of melatonin-medicated JNK3 and Arrb1 expression.Results: In this study, we found out melatonin contributed to the ameloblastic mineralization, from which we can observed the elevated expression of enamel matrix protein, and increased ALP activity and mineralized nodules formation. RNA-seq analysis showed the up-regulation of neural JNK3 and down-regulation of Arrb1 in ALCs. Meanwhile, phosphorylated JNK3 deficiency (phosphorylated JNK3 inhibitor---SR3576 added to culture medium) led to mineralization delay, and Arrb1 overexpression proved Arrb1 takes bridge between melatonin receptors (MTNR) and JNK3 in MAPK signaling pathway.

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.

Multiple-replicon resistance plasmids have become important carriers of resistance genes in Gram-negative bacteria, and the evolution of multiple-replicon plasmids is still not clear. Here, 56 isolates of Klebsiella isolated from different wild animals and environments between 2018 and 2020 were identified by phenotyping via the micro-broth dilution method and were sequenced and analyzed for bacterial genome-wide association study. Our results revealed that the isolates from non-human sources showed more extensive drug resistance and especially strong resistance to ampicillin (up to 80.36%). The isolates from Malayan pangolin were particularly highly resistant to cephalosporins, chloramphenicol, levofloxacin, and sulfamethoxazole. Genomic analysis showed that the resistance plasmids in these isolates carried many antibiotic resistance genes. Further analysis of 69 plasmids demonstrated that 28 plasmids were multiple-replicon plasmids, mainly carrying beta-lactamase genes such as blaCTX–M–15, blaCTX–M–14, blaCTX–M–55, blaOXA–1, and blaTEM–1. The analysis of plasmids carried by different isolates showed that Klebsiella pneumoniae might be an important multiple-replicon plasmid host. Plasmid skeleton and structure analyses showed that a multiple-replicon plasmid was formed by the fusion of two or more single plasmids, conferring strong adaptability to the antibiotic environment and continuously increasing the ability of drug-resistant isolates to spread around the world. In conclusion, multiple-replicon plasmids are better able to carry resistance genes than non-multiple-replicon plasmids, which may be an important mechanism underlying bacterial responses to environments with high-antibiotic pressure. This phenomenon will be highly significant for exploring bacterial resistance gene transmission and diffusion mechanisms in the future.

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been proven effective in post-stroke motor function enhancement, yet whether the combination of MI-BCI and tDCS may further benefit the rehabilitation of motor functions remains unknown. This study investigated brain functional activity and connectivity changes after a 2 week MI-BCI and tDCS combined intervention in 19 chronic subcortical stroke patients. Patients were randomized into MI-BCI with tDCS group and MI-BCI only group who underwent 10 sessions of 20 min real or sham tDCS followed by 1 h MI-BCI training with robotic feedback. We derived amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) from resting-state functional magnetic resonance imaging (fMRI) data pre- and post-intervention. At baseline, stroke patients had lower ALFF in the ipsilesional somatomotor network (SMN), lower ReHo in the contralesional insula, and higher ALFF/Reho in the bilateral posterior default mode network (DMN) compared to age-matched healthy controls. After the intervention, the MI-BCI only group showed increased ALFF in contralesional SMN and decreased ALFF/Reho in the posterior DMN. In contrast, no post-intervention changes were detected in the MI-BCI + tDCS group. Furthermore, higher increases in ALFF/ReHo/FC measures were related to better motor function recovery (measured by the Fugl-Meyer Assessment scores) in the MI-BCI group while the opposite association was detected in the MI-BCI + tDCS group. Taken together, our findings suggest that brain functional re-normalization and network-specific compensation were found in the MI-BCI only group but not in the MI-BCI + tDCS group although both groups gained significant motor function improvement post-intervention with no group difference. MI-BCI and tDCS may exert differential or even opposing impact on brain functional reorganization during post-stroke motor rehabilitation; therefore, the integration of the two strategies requires further refinement to improve efficacy and effectiveness.

We report epidemiologic, laboratory, and clinical findings for 7 patients with 2019 novel coronavirus disease in a 2-family cluster. Our study confirms asymptomatic and human-to-human transmission through close contacts in familial and hospital settings. These findings might also serve as a practical reference for clinical diagnosis and medical treatment.

Summary: Nonrandom DNA segregation (NDS) is a mitotic event in which sister chromatids carrying the old (parent) DNA strands are distributed exclusively to one of the two daughter cells. Although this phenomenon occurs in multiple organisms, the low frequency poses an obstacle to observation. Here, we present an improved protocol to induce NDS under replication stress. This protocol can be modified to accommodate various cell lines.For complete details on the use and execution of this protocol, please refer to Xing et al. (2020).

Objective To investigate the related risk factors and predictive nomogram of postoperative hypoxaemia in elderly patients with femoral neck fractures. Methods This study included patients aged ≥65 years who underwent surgical treatment of acute femoral neck fractures. Univariate and multivariate logistic analyses were performed to determine the incidence of and risk factors for postoperative hypoxaemia. A predictive nomogram was constructed based on the multivariable model. Using the bootstrap method, discrimination was determined by the C-index and calibration plot. Results The logistic regression analysis showed that the anaesthesia type, surgical procedure, American Society of Anesthesiologists (ASA) classification, preoperative hypoxaemia occurrence, and age were independent predictors of development of postoperative hypoxaemia. The predictive formula for hypoxaemia was established as follows: hypoxaemia=−0.8668×spinal anaesthesia (whether)+0.1162×nerve anaesthesia (whether)+1.9555×plate/screw fixation (whether)+1.4950×hip replacement (whether)+0.4883×ASA classification+1.7153×preoperative oxygenation index+0.1608×age. With the bootstrap method, the prediction curve fit well with the ideal curve, suggesting that the prediction curve constructed in this study has good predictive ability. Conclusions Anaesthesia type, surgical procedure, ASA classification, preoperative hypoxaemia occurrence, and age were risk factors for postoperative hypoxaemia in elderly patients with femoral neck fractures. The predictive nomogram was designed for preoperative assessment of the risk of postoperative hypoxaemia by calculating the risk score.

Due to its drug resistant nature, β-lactamase represents a serious challenge for public health. Extended-spectrum β-lactamase (ESBL) producing Klebsiella pneumoniae clones are increasingly reported worldwide. Little is known about the prevalence and biological characteristics of drug-resistant strains in zoos. During routine surveillance at the Zhengzhou Zoo of China, we found Klebsiella pneumoniae isolate in healthy Red Kangaroos (Macropus Rufus) with severe MDR. The Klebsiella pneumoniae were especially resistant to Cefuroxime Sodium (MIC, > 64 μg/mL), Ceftriaxone (MIC, >8 μg/mL) and Cefepime (MIC, >64 μg/mL), and belonged to ST290. Subsequently, whole genome sequencing (WGS) showed that the Chrome Chr-M297-1 harbored blaDHA–3, blaSHV–1, blaCTX–M–14, fosA5, dfrA3, sul3, etc., and pM297-1.1 [222,864 bp, IncFIB(K)], which carried nine antimicrobial genes including blaCTX–M–14, blaTEM–191, aph(3″)-Ib, aph(6)-Id and qnrS1, etc., and pM297-1.2 [225,763 bp, IncFII(K)] carried 22 antimicrobial genes including blaTEM–1, blaCTX–M–3, aph(3′)-Ia, aac(3)-IIa, aac(6′)-Ib-cr, aadA16, qnrB2, qnrS1, qacEΔ1, mphA, sul1, and dfrA27, etc. A traceability analysis then revealed that these two plasmids were highly similar to those recovered from human clinical samples in some southern cities in Sichuan Province, China (>99%), suggesting that these plasmids are spreading in China. Furthermore, two plasmids harboring conjugal transfer genes facilitated the transmission of antimicrobial genes by conjugation with E. coli J53. Our research shows that the transmission and adaptation of Klebsiella pneumoniae producing ESBLs is occurring in zoo environments, suggesting that zoos may be becoming important potential reservoirs for clinically important drug-resistant genes. It is therefore necessary to monitor the emergence and spread of drug-resistant gene strains in captive wild animals held in zoo environments.

The active layer thickness (ALT) in permafrost regions regulates hydrological cycles, water sustainability, and ecosystem functions in the cryosphere and is extremely sensitive to climate change. Previous studies often focused on the impacts of rising temperature on the ALT, while the roles of soil water content and soil granularity have rarely been investigated. Here, we incorporate alterations of soil water contents in soil thermal properties across various soil granularities and assess spatiotemporal ALT dynamics on the Qinghai-Tibet Plateau (QTP). The regional average ALT on the QTP is projected to be nearly 4 m by 2100. Our results indicate that soil wetting decelerates the active layer thickening in response to warming, while latent heat exerts stronger control on ALTs than thermal conductivity does. Under similar warming conditions, active layers thicken faster in coarse soils than in fine soils. An important ramification of this study is that neglecting soil wetting may cause overestimations of active layer thickening on the QTP.

Previous studies have found that circular RNA (circRNA) hsa_circ_0026827 plays a role during osteoblast differentiation, but the mechanism is unclear. The aim of this study was to illuminate the role of hsa_circ_0026827 in human dental pulp stem cells (DPSCs) during osteoblast differentiation. The results show that hsa_circ_0026827 expression significantly increased during osteoblast differentiation, while knockdown of hsa_circ_0026827 suppressed DPSC-derived osteoblast differentiation. microRNA (miRNA) expression profile analysis showed that downregulation of hsa_circ_0026827 promoted miR-188-3p expression. miR-188-3p downregulation restored osteogenic differentiation of DPSCs after hsa_circ_0026827 was silenced. Luciferase reporter assays verified that miR-188-3p was the target of hsa_circ_0026827 and also demonstrated that Beclin1 and RUNX1 were miR-188-3p downstream targets. miR-188-3p overexpression suppressed DPSC osteogenic differentiation by targeting Beclin-1-mediated autophagy and runt-related transcription factor 1 (RUNX1). In vivo studies using a heterotopic bone model also found that hsa_circ_0026827 overexpression plays an important role in promoting heterotopic bone formation. In conclusion, our research indicates that hsa_circ_0026827 promotes osteoblast differentiation of DPSCs via Beclin1 and the RUNX1 signaling pathways by sponging miR-188-3p, which suggests novel therapeutics for osteoporosis treatment.

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0-54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P

Circular RNAs (circRNAs) have been found to be a crucial role in stem cell-associated bone regeneration. However, the functions and underlying mechanisms of circRNAs in the osteogenic differentiation of human dental pulp stem cells (hDPSCs) remain largely unclear. We found that overexpression of circRNA124534 unexpectedly promoted DPSCs osteogenesis in vitro and in vivo. Our results confirmed circRNA124534, acting as a miRNA sponge, directly interacts with miR-496 and consequently regulates β-catenin, which in turn exerts osteogenesis of DPSCs. Enforced expression of miR-496 reversed the osteogenesis of circRNA124534, and suppression of miR-496 enhanced the osteogenic differentiation of DPSCs by promoting β-catenin. In conclusion, our findings demonstrate functions of circRNA124534 in modulating osteogenic differentiation through the miR-496/β-catenin pathway; thus, providing a novel potential target for therapy.

Abstract Background Traditional incision repair and minimally invasive repair for acute Achilles tendon repair have limitations. This study aimed to present our series of 23 patients with acute Achilles tendon rupture that was repaired using two small incisions to assist the anchor repair of the tear and a new “circuit” suture technique. Methods This was a retrospective study of 23 patients with acute Achilles tendon rupture treated with the new technique at Changhai Hospital between January 2015 and December 2016 and followed up for 14–33 months. Clinical outcome was assessed using the AOFAS, Leppilahti, and Arner-Lindholm scores. Complications, range of motion (ROM), and time to return to work and light sport activity were assessed. Results The AOFAS score was 85–96 at 3 months and 92–100 at 12 months. The 3-month ROM was 27°–37°, and the 12-month ROM was 36°–48°. The Leppilahti score was 85–95 at 3 months and 90–100 at 12 months. The recovery time of the patients was 10–18 weeks. The postoperative recovery time to exercise was 16–24 weeks. There was only one case of deep venous thrombosis. According to the Arner-Lindholm assessment criteria, patient outcomes were rated as excellent in 20 (87.0%) cases, good in three (13.0%) cases, and poor in 0 cases. The excellent-to-good rate was 100%. Conclusion The limited-open procedure combined with a single-anchor and “circuit” suture technique could be used to repair torn Achilles sites, with a low occurrence of complications. This new and minimally invasive technique could be an alternative in the management of acute Achilles tendon rupture.