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Abstract Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P

Abstract Fibroblast growth factor 2 (FGF2) is a crucial factor in odontoblast differentiation and dentin matrix deposition, which facilitates pulpodentin repair and regeneration. Nevertheless, the specific biological function of FGF2 in odontoblastic differentiation remains unclear because it is controlled by complex signalling pathways. This study aimed to investigate the mechanism underlying the effect of FGF2 on osteo/odontogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were pretreated with conditioned media containing FGF2 for 1 week, followed by culturing in induced differentiation medium for another week. RNA sequencing (RNA-seq) combined with quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the pathways affected by FGF2 in SCAP. Osteo/odontogenic differentiation of SCAP was determined using Alizarin red S staining, alkaline phosphatase staining, RT-qPCR, and western blotting. Pretreatment with FGF2 for 1 week increased the osteo/odontogenic differentiation ability of SCAP. RNA-seq and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that phosphatidylinositol 3-kinase (PI3K)/AKT signalling is involved in the osteogenic function of FGF2. RT-qPCR results indicated that SCAP expressed FGF receptors, and western blotting showed that p-AKT was reduced in FGF2-pretreated SCAP. The activation of the PI3K/AKT pathway partially reversed the stimulatory effect of FGF2 on osteo/odontogenic differentiation of SCAP. Our findings suggest that pretreatment with FGF2 enhances the osteo/odontogenic differentiation ability of SCAP by inhibiting the PI3K/AKT pathway.

Abstract Background Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. Methods Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children’s Medical Center of Peking University First Hospital from September 2014 to August 2023. Results Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing. Conclusions Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1.

Heterostructured ferritic steels with bimodal-grained lamellar (BG-L) and ultrafine-grained lamellar (UFG-L) microstructure were prepared through a warm deformation process. The BG-L steel exhibits enhanced mechanical properties compared to conventional quenched and tempered (QT) steel. While the UFG-L steel demonstrates an outstanding combination of strength, ductility, and toughness. Furthermore, the UFG-L steels exhibit no ductile-to-brittle transition (DBT) from room temperature (RT) to liquid nitrogen temperature (LNT) and the Charpy impact energy remains as high as 314 J at LNT. The enhanced toughness at LNT can be attributed to the crack-arrester mechanism caused by grain-boundary delamination.

Abstract Background Long noncoding RNA thymopoietin-antisense RNA 1 (TMPO-AS1) is recognized as a participant in cancer progression. Nevertheless, its biological function in colorectal cancer remains obscure and needs further elucidation. Methods and Results First, we discovered enriched TMPO-AS1 in the tumor tissues that were related to poor prognosis. TMPO-AS1 knockdown enhanced SW480 cell apoptosis but inhibited invasion, proliferation, migration, and glucose metabolism. Further, MiR-1270 is directly bound with TMPO-AS1. MiR-1270 mimics were confirmed to inhibit cell proliferation, invasion, and glucose metabolism in our study. Mechanistically, miR-1270 directly is bound with the 3' untranslated regions (3'UTR) of PKM2 to downregulate PKM2. MiR-1270 inhibitors reversed the TMPO-AS1 knockdown’s effect on suppressing the tumor cell proliferation, invasion, and glycolysis, while the knockdown of PKM2 further inverted the function of miR-1270 inhibitors on the TMPO-AS1 knockdown. Conclusions This study illustrated that TMPO-AS1 advanced the development and the glycolysis of colorectal cancer by modulating the miR-1270/PKM2 axis, which provided a new insight into the colorectal cancer therapeutic strategy.

Artificial intelligence can be indirectly applied to the repair of peripheral nerve injury. Specifically, it can be used to analyze and process data regarding peripheral nerve injury and repair, while study findings on peripheral nerve injury and repair can provide valuable data to enrich artificial intelligence algorithms. To investigate advances in the use of artificial intelligence in the diagnosis, rehabilitation, and scientific examination of peripheral nerve injury, we used CiteSpace and VOSviewer software to analyze the relevant literature included in the Web of Science from 1994–2023. We identified the following research hotspots in peripheral nerve injury and repair: (1) diagnosis, classification, and prognostic assessment of peripheral nerve injury using neuroimaging and artificial intelligence techniques, such as corneal confocal microscopy and coherent anti-Stokes Raman spectroscopy; (2) motion control and rehabilitation following peripheral nerve injury using artificial neural networks and machine learning algorithms, such as wearable devices and assisted wheelchair systems; (3) improving the accuracy and effectiveness of peripheral nerve electrical stimulation therapy using artificial intelligence techniques combined with deep learning, such as implantable peripheral nerve interfaces; (4) the application of artificial intelligence technology to brain-machine interfaces for disabled patients and those with reduced mobility, enabling them to control devices such as networked hand prostheses; (5) artificial intelligence robots that can replace doctors in certain procedures during surgery or rehabilitation, thereby reducing surgical risk and complications, and facilitating postoperative recovery. Although artificial intelligence has shown many benefits and potential applications in peripheral nerve injury and repair, there are some limitations to this technology, such as the consequences of missing or imbalanced data, low data accuracy and reproducibility, and ethical issues (e.g., privacy, data security, research transparency). Future research should address the issue of data collection, as large-scale, high-quality clinical datasets are required to establish effective artificial intelligence models. Multimodal data processing is also necessary, along with interdisciplinary collaboration, medical-industrial integration, and multicenter, large-sample clinical studies.

ABSTRACTThe low-temperature aging treatment at 250°C can significantly improve the tensile superelasticity of NiTi alloys fabricated by electron beam directed energy deposition (EB-DED). However, it requires a very long aging duration (up to 200 h) to achieve excellent tensile superelasticity due to inherent coarse grain size. To accelerate the aging process, the high-density dislocations are introduced by artificial thermal cycling treatment prior to the aging treatment (the original dislocation content in EB-DED processed NiTi alloys is very low), which will promote the subsequent uniform precipitation of nanoscale Ni4Ti3 particles during low-temperature aging treatment. The phase transformation behaviour always maintains a stable two-stage martensitic phase transformation. Under a cyclic tensile test at 6% strain, 24 h aged sample with thermal cycling maintains a recovery rate exceeding 90% even after 10 cycles, comparable to the performance of the sample aged for 200 h without thermal cycling, indicating a substantial improvement in aging efficiency.

Abstract Understanding multiple-factor effects on particle size selectivity by extreme rainfall events in Ala-Shan Gobi desert is of great significance for better estimation of potential Asian dust emission sources. Artificial rainfall simulation experiments were used to investigate the particle size selectivity characteristics by extreme rainfall events under different rainfall intensities (20 mm h−1 and 40 mm h−1), slope gradients (3° and 15°) and gravel coverages (0, 30%, and 60%). Moreover, the relations of clay content (Clc), silt content (Sic), fine particle (

To control the microstructure and improve the mechanical properties of Mn–Cu alloy additive manufacturing components, this work adopts various scanning strategies (rotations of 0°, 45°, 67°, and 90° between successive layers) to change the heat input distribution and heat dissipation. The results show that the scanning strategies can impact the porosity, cracks, grain size, and grain growth direction of Mn–Cu alloy additive manufacturing parts. By adjusting scanning strategies to change the heat flow direction the columnar-to-equiaxed transition can be achieved. The samples exhibit minimal cracks and pores (porosity of 0.0006 %). Using a scanning rotation angle of 67° during processing, the maximum tensile strength can reach 510 MPa with a 29 % elongation, attributed to effective grain refinement and a high dislocation density. This study demonstrates the feasibility of grain refinement and improved mechanical properties for the Mn–Cu alloys by changing the scanning strategies.

Understanding the spatial and temporal differentiation of ecosystem service value (ESV) brought about by land use/land cover (LULC) transformation is of significance to the ecosystem management policy making and decision supports. In this research, the upper basin of Miyun Reservoir in northern Beijing was chosen as study area because of its importance to ecological security of Beijing, the Capital City of China. The equivalent factor method was used to evaluate the ESV, and the responses of spatial and temporal variations of ESV to LULC transformations were explored by gridding and spatial autocorrelation analysis during years 1990–2020. The results indicate that the total ESV increase from 19.367 billion Yuan to 20.419 billion Yuan during 1990–2020. Forest is the most significant LULC type to ESV, contributing over 85% to the total ESV each year and contributing more than 50% to the changes of ESV. The continuous transformation of grassland, cropland and shrub to forest is the main reason for the increase in total ESV in the study area. The geographical distribution of LULC directly influences the spatial distribution characteristics of ESV, resulting in a strong spatial positive autocorrelation of ESV. The spatial and temporal variations of LULC and ESV around Miyun Reservoir reflect the significant conflict between human activities and ecological protection. The recommendation is to limit the expansion of construction land and cropland with high efficiency and to expand forest and water to continuously increase ESV. This study provides support for land use planning, ecological health and environmental protection in the upper basin of Miyun Reservoir in Beijing, as well as methodological references for exploration in hilly areas facing the conflict between economic development and ecological protection.

To investigate the periodic disturbance and damage characteristics of coal under different impact pressures, the stress‒strain failure and damage trends of weak, impact-prone coal samples were analysed under different impact pressures and different numbers of impacts. Split-Hopkinson pressure bar (SHPB) tests were conducted to study the stress‒strain curve, dynamic compressive strength, elastic modulus, failure strain, and absorbed energy responses with different numbers of impacts and different strain rates. Fractal theory and methods were applied to analyse the influence of different impact pressures and different numbers of impacts on coal sample failure to reveal the relationship between the number of impacts and the fractal size characteristics of coal fragmentation. The energy modes and failure modes of coal samples under different impact effects were analysed under dynamic loading. Regarding the energy absorption corresponding to different numbers of impacts, the energy absorption per unit volume (EAPUV) of three impacts was calculated to be 0.46 J/cm3. The number of impacts was directly correlated with the energy absorbed by the coal sample. Furthermore, the number of impacts was directly correlated with the severity of the deformation and damage of the coal sample and was inversely correlated with the fragmentation of the coal sample. The degree of coal sample fragmentation was directly proportional to the number of impacts, and the fractal dimension increased with the number of impacts. The study of the failure and fractal characteristics of coal samples under different impact pressures and different numbers of impacts provides important information for the prevention and control of coal mine rock bursts.

Abstract Background Colorectal cancer (CRC), known as prevalent cancer, has risen to be the leading cause of cancer‐related death. Engineered exosomes had attracted much attention since they acted as carriers to deliver small molecule drugs, therapeutic nucleic acids, and polypeptides to treat a series of cancers. Methods and Results Here, we found that the PKH‐26 labeled exosomes, which were derived from the CRC cells, could be efficiently absorbed by SW1116 cells and had an abundant fluorescence distribution in tumors, compared with the exosomes derived from mesenchymal stem cells (MSC) and HepG2 cells. This Research demonstrated that engineered CRC‐exosomes loaded with functional miR‐1270 (Exo‐miR‐1270) enriched in miR‐1270 strongly inhibited the proliferation by CCK‐8 and EdU assays, migration by wound‐healing and transwell assays, and promoted the apoptosis for CRC cells through flow cytometry. MiR‐1270 overexpression delivered by CRC exosomes contributed to inhibiting the tumor growth potential of CRC in vivo and increasing the overall survival of the mice. Moreover, the safety evaluation results showed that CRC‐exosomes loaded with functional miR‐1270‐mimics had no toxicity for other organs by histopathological analysis and no influence on the vital chemistry and hematology parameters for mice in vivo safety evaluation. Conclusion These results indicate that Exo‐miR‐1270 can effectively treat CRC tumors by intravenous administration. Our work provided a foundation that the homologous tumor‐derived exosomes mediated miRNA delivery for the treatment of CRC.

In order to further improve the atomization and wetting performance of droplets, and increase the control efficiency of fine dust, in this study, the non-wetting anthracite dust in the Jincheng Mine was taken as an example. The method of the combination of the crossover experiments about magnetoelectric property coupled by surface tension, the two-phase flow numerical simulation on spherical droplet-dust particle collision by Comsol and the experiment of dust-reduction efficiency comparison was adopted. By applying the kinetic characteristics of spherical droplet-dust collision to spray dust reduction, the kinetic behaviors of magnetized and charged droplets capturing coal dust particles were investigated, and the dust suppression mechanism of magneto-electric coupled water mist was revealed. The results show that there is no linear positive correlation between magnetisation strength and droplet surface tension. The relationship between magnetisation, charge and magneto-electric coupling ability to improve droplet wettability is as follows: magneto-electric coupling>charge>magnetisation. For magnetoelectric spray, there exist optimum coupling parameters. When the magnetization intensity is 300 MT and the charge voltage is 8 kV, the surface tension of the droplet is the minimum (9.20 mN/m). In the process of collision between spherical droplets and coal dust particles, magneto-electric coupling eliminates the adverse effects of changes in relative collision velocity and particle-size-ratio on that droplets capture coal dust particles. At this time, the magnetoelectric droplets will not rebound on the surface of the coal dust particles. Compared with the normal droplets, the magnetoelectric droplets are more likely to split and produce satellite droplets. Therefore, the atomization performance is improved, the concentration of fine droplets is increased and the probability of the collision between droplets and coal dust particles is increased. Moreover, the surface tension and viscosity of the magnetoelectric droplets are reduced, and the spreading range on the surface of coal dust particles is expanded by 44.98%, which improves the atomization and wetting performance of droplets. By comparing the dust reduction effect of magnetoelectric water mist with ordinary water mist, it was found that the reduction efficiency of the full dust and the respirable dust for magneto-electric water mist reached 94.07% and 82.69% respectively, which increased by 39.16% and 42.29% respectively.

Abstract Background Circulating tumor cells (CTCs), an indispensable liquid biopsy classifier, can provide extra information for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Methods We systematically analyzed the peripheral blood of preoperative HCC patients (n = 270) for CTC number, Ki67 index reflecting the proliferative CTC percentage (PCP), and CTC clusters correlated with the characteristics of malignant HCC tumors. Results Driver gene mutations were found with high levels of consistency between CTCs and primary tumors (n = 73). CTC number and PCP were associated with tumor size, microvascular invasion (MVI), presence or absence of multiple tumors, and thrombosis significantly. CTC number and PCP robustly separated patients with and without relapse, with a sensitivity of 88.89%/81.48% and a specificity of 72.73%/94.81% in the training set (n = 104) and corresponding values of 80.00%/86.67% and 78.38%/89.19% in the validation set (n = 52), showing a better performance than that associated with the alpha‐fetoprotein (AFP) level. CTC number, PCP, CTC clusters, and MVI were independent significant risk factors for HCC recurrence (P = 0.0375, P

Abstract Aims To test the relationship between practice environment and turnover intention, considering the moderation of perceived organizational support (POS) and the mediation of general well‐being (GWB) and occupational burnout (OB) among the nurse population. Design A cross‐sectional survey design. Methods Based on a sample of 474 nurses from two hospitals between May 2020 and September 2021, a moderated multi‐mediation model was tested in which GWB and OB served as two mediators between practice environments and nurses' turnover intention, and POS was regarded as a moderator between practice environments and GWB. Results This current study supported a moderated multi‐mediation model where the relationship between practice environment and turnover intention (B = 0.33, p

The recent outbreak of the coronavirus disease 2019 (COVID-19) pandemic and the continuous evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have highlighted the significance of new detection methods for global monitoring and prevention. Although quantitative reverse transcription PCR (RT-qPCR), the current gold standard for diagnosis, performs excellently in genetic testing, its multiplexing capability is limited because of the signal crosstalk of various fluorophores. Herein, we present a highly efficient platform which combines 17-plex assays with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), enabling the targeting of 14 different mutation sites of the spike gene. Diagnosis using a set of 324 nasopharyngeal swabs or sputum clinical samples with SARS-CoV-2 MS method was identical to that with the RT-qPCR. The detection consistency of mutation sites was 97.9% (47/48) compared to Sanger sequencing without cross-reaction with other respiratory-related pathogens. Therefore, the MS method is highly potent to track and assess SARS-CoV-2 changes in a timely manner, thereby aiding the continuous response to viral variation and prevention of further transmission.

Fungi are highly widespread and commonly colonize multicellular organisms that live in natural environments. Notably, studies on viruses infecting plant-associated fungi have revealed the interesting phenomenon of the cross-kingdom transmission of viruses and viroids from plants to fungi. This implies that fungi, in addition to absorbing water, nutrients, and other molecules from the host, can acquire intracellular parasites that reside in the host. These findings further suggest that fungi can serve as suitable alternative hosts for certain plant viruses and viroids. Given the frequent coinfection of fungi and viruses in humans/animals, the question of whether fungi can also acquire animal viruses and serve as their hosts is very intriguing. In fact, the transmission of viruses from insects to fungi has been observed. Furthermore, the common release of animal viruses into the extracellular space (viral shedding) could potentially facilitate their acquisition by fungi. Investigations of the cross-infection of animal viruses in fungi may provide new insights into the epidemiology of viral diseases in humans and animals.

FOXO3a is a protein of the forkhead box family that inhibits tumour cell growth. One of the regulatory modes affecting the role of FOXO3a is microRNA targeting and degradation of its mRNA expression, and conversely, aberrant expression of FOXO3a as a transcription factor also influences microRNA levels. We summarized the results of the regulatory interactions of twenty-five microRNAs with FOXO3a in five types of malignant tumours and found that dual microRNAs synergize with FOXO3a to inhibit breast cancer cell growth including two groups; Three individual microRNAs collaborated with FOXO3a to restrain hepatocellular carcinoma progression; Twelve individual microRNAs antagonized FOXO3a to promote the development of a single tumour cell, respectively; and five microRNAs antagonized FOXO3a to contribute to the progression of more than two types of tumours. The above findings demonstrated the tumour suppressor effect of FOXO3a, but another result revealed that miR-485-5p and miR-498 inhibited the growth of hepatocellular carcinoma cells by antagonizing FOXO3a when acting in combination with other long-stranded non-coding RNAs, respectively, suggesting that FOXO3a at this moment plays the function of promoting the tumour progression. The PI3K/AKT, Snail, VEGF-NRP1, and Wnt/β-catenin signalling pathways perform crucial roles in the above process. It is anticipated that the above studies will assist in understanding the effects of FOXO3a-MicroRNA interactions in cancer genesis and development, and provide new perspectives in the treatment of malignant tumours.

BackgroundMost people are infected with COVID-19 during pandemics at the end of 2022. Older patients were more vulnerable. However, the incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection is not well described in elderly hospitalized COVID-19 patients.MethodsWe retrospectively reviewed the medical records of all elderly (≥65 years) hospitalized patients with laboratory-confirmed COVID-19 from December 1, 2022 to January 31, 2023. Demographics, underlying diseases, treatments, and laboratory data were collected. Univariate and multivariate logistic regression models were used to explore the risk factors associated with secondary bacterial, fungal or viral pulmonary infection and co-infection.ResultsA total of 322 older patients with COVID-19 were enrolled. The incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection was 27.3% (88/322) and 7.5% (24/322), respectively. The overall in-hospital mortality of all patients was 32.9% (106/322), and the in-hospital mortality among patients who acquired with secondary pulmonary infection and co-infection was 57.0% (57/100). A total of 23.9% (77/322) of patients were admitted to ICU within 48 h of hospitalization. The incidence of secondary pulmonary infection and co-infection among patients admitted to the ICU was 50.6% (39/77) and 13.0% (10/77), respectively. The overall in-hospital mortality of ICU patients was 48.1% (37/77), and the in-hospital mortality of ICU patients acquired with secondary pulmonary infection and co-infection was 61.4% (27/44). A total of 83.5% (269/322) of the included patients received empirical antibiotic therapy before positive Clinical Microbiology results. Influenza A virus (the vast majority were the H3N2 subtype) was the most common community acquired pathogen for co-infection. While A. baumannii, K. pneumoniae, and P. aeruginosa were the common hospital acquired pathogens for co-infection and secondary pulmonary infection. The incidence of Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections was high, and the mortality reached 76.9%. Predictors of secondary pulmonary infection and co-infection were ICU admission within 48 h of hospitalization, cerebrovascular diseases, critical COVID-19, and PCT > 0.5 ng/mL.ConclusionThe prognosis for elderly hospitalized COVID-19 patients with secondary pulmonary infection or co-infection is poor. The inflammatory biomarker PCT > 0.5 ng/mL played an important role in the early prediction of secondary pulmonary infection and co-infection in COVID-19 patients.

Abstract Viral infection commonly induces autophagy, leading to antiviral responses or conversely, promoting viral infection or replication. In this study, using the experimental plant Nicotiana benthamiana, we demonstrated that the rice stripe virus (RSV) coat protein (CP) enhanced autophagic activity through interaction with cytosolic glyceraldehyde-3-phosphate dehydrogenase 2 (GAPC2), a negative regulator of plant autophagy that binds to an autophagy key factor, autophagy-related protein 3 (ATG3). Competitive pull-down and co-immunoprecipitation (Co-IP)assays showed that RSV CP activated autophagy by disrupting the interaction between GAPC2 and ATG3. An RSV CP mutant that was unable to bind GAPC2 failed to disrupt the interaction between GAPC2 and ATG3 and therefore lost its ability to induce autophagy. RSV CP enhanced the autophagic degradation of a viral movement protein (MP) encoded by a heterologous virus, citrus leaf blotch virus (CLBV). However, the autophagic degradation of RSV-encoded MP and RNA-silencing suppressor (NS3) proteins was inhibited in the presence of CP, suggesting that RSV CP can protect MP and NS3 against autophagic degradation. Moreover, in the presence of MP, RSV CP could induce the autophagic degradation of a remorin protein (NbREM1), which negatively regulates RSV infection through the inhibition of viral cell-to-cell movement. Overall, our results suggest that RSV CP induces a selective autophagy to suppress the antiviral factors while protecting RSV-encoded viral proteins against autophagic degradation through an as-yet-unknown mechanism. This study showed that RSV CP plays dual roles in the autophagy-related interaction between plants and viruses.

Abstract Aim This study aimed to systematically characterize transplant rejection after immune checkpoint inhibitors (ICIs) initiation in solid organ transplant recipients (SOTRs). Methods Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database and case reports in the literature. Disproportionality analysis including information component and reported odds ratio (ROR) was performed to access potential risk signals. Results A total of 168 patients with transplant rejection after ICIs usage were identified in the FAERS database, and 89 cases were identified in the literature review. ICIs were significantly associated with transplant rejection (ROR025: 2.2). A strong risk signal was found for combination therapy with pembrolizumab and ipilimumab compared to monotherapy. Conclusion Immune checkpoint inhibitors were significantly associated with transplant rejection in SOTRs.

Fire blight, caused by the bacterium Erwinia amylovora, is a major threat to pear production worldwide. Bacteriophages, viruses that infect bacteria, are a promising alternative to antibiotics for controlling fire blight. In this study, we isolated a novel bacteriophage, RH-42-1, from Xinjiang, China. We characterized its biological properties, including host range, plaque morphology, infection dynamics, stability, and sensitivity to various chemicals. RH-42-1 infected several E. amylovora strains but not all. It produced clear, uniform plaques and exhibited optimal infectivity at a multiplicity of infection (MOI) of 1, reaching a high titer of 9.6 × 109 plaque-forming units (PFU)/mL. The bacteriophage had a short latent period (10 min), a burst size of 207 PFU/cell, and followed a sigmoidal one-step growth curve. It was stable at temperatures up to 60 °C but declined rapidly at higher temperatures. RH-42-1 remained viable within a pH range of 5 to 9 and was sensitive to extreme pH values. The bacteriophage demonstrates sustained activity upon exposure to ultraviolet radiation for 60 min, albeit with a marginal reduction. In our assays, it exhibited a certain level of resistance to 5% chloroform (CHCl3), 5% isopropanol (C3H8O), and 3% hydrogen peroxide (H2O2), which had little effect on its activity, whereas it showed sensitivity to 75% ethanol (C2H5OH). Electron microscopy revealed that RH-42-1 has a tadpole-shaped morphology. Its genome size is 14,942 bp with a GC content of 48.19%. Based on these characteristics, RH-42-1 was identified as a member of the Tectiviridae family, Alphatectivirus genus. This is the first report of a bacteriophage in this genus with activity against E. amylovora.

The flapping hydrofoil bionic pump is an innovative hydrodynamic device that utilizes flapping hydrofoil technology. Flapping hydrofoil bionic pumps are crucial in addressing issues like inadequate river hydropower and limited water purification capabilities in flat river network regions. Optimizing the foil characteristics is essential for enhancing the hydrodynamic efficiency of the flapping hydrofoil bionic pump. This study investigates the impact of foil camber parameters on the hydrodynamic performance of swing-type asymmetric flapping bionic pumps. The NACA series standard foils with varying cambers are analyzed using the overlapping grid technology and finite volume method. The thrust coefficient, flow rate, pumping efficiency, and flow field structure of the flapping hydrofoil bionic pump are examined under pressure inlet conditions with the foil camber. The findings indicate that increasing the foil’s curvature within a specific range can greatly enhance the maximum values of thrust coefficient, propulsive efficiency, and pumping efficiency of the flapping hydrofoil bionic pump. Specifically, when the foil curvature is 6%c, the maximum value of the instantaneous thrust coefficient of the flapping hydrofoil bionic pump is significantly improved by 31.25% compared to the symmetric foil type under the condition of an oscillating frequency of f = 1 HZ. The flapping hydrofoil bionic pump achieves its maximum pumping efficiency when the oscillation frequency is within the range of f ≤ 2.5 Hz. This efficiency is 11.7% greater than that of the symmetric foil, and it occurs when the foil curvature is 8%c. Within the frequency range of f > 2.5 Hz, the flapping hydrofoil bionic pump that has a foil curvature of 6%c exhibits the highest enhancement in pumping efficiency. It achieves a maximum increase of 12.8% compared to the symmetric foil type. Nevertheless, the average head was less than 0.4 m, making it suitable for ultra-low-head applications.

In this work, the nanostructure of oxide dispersion-strengthened steels was studied by small-angle neutron scattering (SANS), transmission electron microscopy (TEM), and atom probe tomography (APT). The steels under study have different alloying systems differing in their contents of Cr, V, Ti, Al, and Zr. The methods of local analysis of TEM and APT revealed a significant number of nanosized oxide particles and clusters. Their sizes, number densities, and compositions were determined. A calculation of hardness from SANS data collected without an external magnetic field, or under a 1.1 T field, showed good agreement with the microhardness of the materials. The importance of taking into account two types of inclusions (oxides and clusters) and both nuclear and magnetic scattering was shown by the analysis of the scattering data.

BackgroundGenital inflammation is one of the most frequent clinical complaints among girls, which was easily overlooked by the general public. This study aimed to investigate the patterns and epidemiological characteristics of pediatric and adolescent female genital inflammation in China.MethodsA retrospective observational study (2011 to 2018) was conducted among all female patients under the age of 0–18 years at the Department of Pediatric and Adolescent Gynecology of The Children’s Hospital, Zhejiang University School of Medicine. Data were collected from the electronic medical records. The abnormal vaginal discharge of patient was collected for microbiological investigation by bacterial and fungal culture. Descriptive analysis was conducted to evaluate the genital inflammation pattern and epidemiological characteristics, including age, season, and type of infected pathogens.ResultsA total of 49,175 patients met the eligibility criteria of genital inflammation and 16,320 patients later came to the hospital for follow-up over the study period. The number of first-visit increased gradually from 3,769 in 2011 to 10,155 in 2018. The peak age of the first visit was 0–6 years old. Non-specific vulvovaginitis, lichen sclerosis, and labial adhesion were the top three genital inflammation. Among the top five potential common pathogens of vaginal infection, the prevalence of Haemophilus influenzae cases was the highest (31.42%, 203/646), followed by Streptococcus pyogenes (27.74%, 176/646), Candida albicans (14.09%, 91/646), Escherichia coli (8.51%, 55/646), and Staphylococcus aureus (6.35%, 41/636). The specific disease categories and pathogens of genital inflammation vary by age groups and season.ConclusionOur study summarizes the pattern of pediatric and adolescent female genital inflammation over an 8-year period in China, emphasizing the need for more public awareness, healthcare services and research in this field.

A wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.

ABSTRACT Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a considerable threat to global public health. This study developed and evaluated a rapid, low-cost, expandable, and sequencing-free high-resolution melting (HRM) assay for the direct detection of SARS-CoV-2 variants. A panel of 64 common bacterial and viral pathogens that can cause respiratory tract infections was employed to evaluate our method’s specificity. Serial dilutions of viral isolates determined the sensitivity of the method. Finally, the assay’s clinical performance was assessed using 324 clinical samples with potential SARS-CoV-2 infection. Multiplex HRM analysis accurately identified SARS-CoV-2 (as confirmed with parallel reverse transcription-quantitative PCR [qRT-PCR] tests), differentiating between mutations at each marker site within approximately 2 h. For each target, the limit of detection (LOD) was lower than 10 copies/reaction (the LOD of N, G142D, R158G, Y505H, V213G, G446S, S413R, F486V, and S704L was 7.38, 9.72, 9.96, 9.96, 9.50, 7.80, 9.33, 8.25, and 8.25 copies/reaction, respectively). No cross-reactivity occurred with organisms of the specificity testing panel. In terms of variant detection, our results had a 97.9% (47/48) rate of agreement with standard Sanger sequencing. The multiplex HRM assay therefore offers a rapid and simple procedure for detecting SARS-CoV-2 variants. IMPORTANCE In the face of the current severe situation of increasing SARS-CoV-2 variants, we developed an upgraded multiplex HRM method for the predominant SARS-CoV-2 variants based on our original research. This method not only could identify the variants but also could be utilized in subsequent detection of novel variants since the assay has great performance in terms of flexibility. In summary, the upgraded multiplex HRM assay is a rapid, reliable, and economical detection method, which could better screen prevalent virus strains, monitor the epidemic situation, and help to develop measures for the prevention and control of SARS-CoV-2.

Summary Coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has recently posed a significant threat to global public health. The objective of this study was to develop and evaluate a rapid, expandable and sequencing‐free high‐resolution melting (HRM) approach for the direct detection and classification of SARS‐CoV‐2. Thirty‐one common pathogens that can cause respiratory tract infections were used to evaluate the specificity of the method. Synthetic RNA with serial dilutions was utilized to determine the sensitivity of the method. Finally, the clinical performance of the method was assessed using 290 clinical samples. The one‐step multiplex HRM could accurately identify SARS‐CoV‐2 and differentiate mutations in each marker site within approximately 2 h. For each target, the limit of detection was lower than 10 copies/reaction, and no cross‐reactivity was observed among organisms within the specificity testing panel. The method showed good uniformity for SARS‐CoV‐2 detection with a consistency of 100%. Regarding the clade classification performance, the results showed good concordance compared with sequencing, with the rate of agreement being 95.1% (78/82). The one‐step multiplex HRM method is a rapid method for SARS‐CoV‐2 detection and classification.

On January 15th, 2022, a submarine volcano in Tonga erupted violently and explosively, ejecting a large amount of ash, gas and water vapor which entered the stratosphere to form a huge ash cloud. The volcanic eruption caused widespread concern at home and abroad. This paper presents a comprehensive analysis of the geological background, eruption history, eruption process, disaster impact, and eruption mechanism of the Tonga Volcano. This draws attention to the current activity of active volcanoes in China, especially to Changbaishan Tianchi volcano, which is the largest active volcano with most potentially catastrophic eruption risk. It warns us that we should take precautionary measures to further strengthen the monitoring and early warning of domestic volcanic hazards. Drawing on the experience of this volcanic disaster in Tonga, it is particularly important to scientifically study and judge the dynamics of volcanoes and improve the domestic volcanic disaster risk monitoring and early warning system.

Abstract Background Acetaminophen (APAP) overdose is a major cause of the morbidity of acute liver failure. The current clinically approved treatment for APAP poisoning, N-acetylcysteine (NAC), has a limited therapeutic window, and prolonged treatment with NAC delays liver regeneration. Mesenchymal stem cells (MSCs) also have therapeutic effects on APAP-induced mouse liver failure, but whether the effects are comparable to those of NAC has not been determined, and the mechanism still needs further exploration. Methods Fasted C57BL/6 mice that received 500 mg/kg APAP were treated intravenously with 300 mg/kg NAC or different amounts of MSCs at 2 h after APAP to investigate survival, hepatocyte necrosis and neutrophil/macrophage recruitment. In vitro co-culture was performed to study the anti-necrotic effects of MSCs on the APAP-injured hepatocyte cell line L-O2. Results MSCs dose-dependently rescued the C57BL/6J mice from APAP-induced liver failure, with 87.5% of MSCs (1 × 106) surviving similar to that of NAC (90%). MSC has similar effects on reduced hepatocyte necrosis and granulocytic myeloid-derived suppressor cells (MDSC) infiltration but enhanced the proportion of regenerative monocytic MDSC when compared to NAC. Mechanistically, MSCs attenuate hepatocyte necrosis by secreting hepatocyte growth factor (HGF). When HGF was knocked down, the protective effects of MSCs were reduced on APAP-induced hepatocyte necrosis and mouse liver failure. Conclusions MSCs are comparable to NAC against APAP-induced liver failure by secreting HGF with less regenerative retardation concerns, thus facilitating the application of MSCs in clinical therapy for APAP liver failure.

Abstract Background Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities. Results From 1108 patients who underwent exome sequencing, we identified eight probands with dual molecular diagnosis and variable skeletal deformities. All eight patients had dual diagnosis consisting of two autosomal dominant diseases. A total of 16 variants in 12 genes were identified, 5 of which were of de novo origin. Patients with dual molecular diagnosis presented blended phenotypes of two genetic diseases. Mendelian disorders occurred more than once include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700). Conclusions This study demonstrated the complicated skeletal phenotypes associated with dual molecular diagnosis. Exome sequencing represents a powerful tool to detect such complex conditions.

Computational ghost imaging is a novel technique, which has a wide range of applications in many fields. As a key part of computational ghost imaging, the measurement matrix plays an important role in imaging quality and system practicability. To improve the imaging quality of computational ghost imaging and overcome the poor stability and non-negativity of the measurement matrix, we propose a new construction method for the deterministic measurement matrix based on the difference set modulo subgroup. This method uses an efficient simulated annealing algorithm to search for the difference set modulo subgroup. Then a 0–1 binary measurement matrix can be constructed according to the obtained difference set. We can show that the measurement matrix constructed by this method has low coherence and can satisfy the restricted isometry property. The simulation and experimental results showed that the reconstruction quality of the proposed measurement matrix was equivalent to the Sparse random matrix and better than the Toeplitz and Circulant matrices, which indicates the feasibility of the newly proposed measurement matrix.

Abstract In this study, we aimed at constructing polycaprolactone (PCL) reinforced keratin/bioactive glass composite scaffolds with a double cross-linking network structure for potential bone repair application. Thus, the PCL-keratin-BG composite scaffold was prepared by using keratin extracted from wool as main organic component and bioactive glass (BG) as main inorganic component, through both cross-linking systems, such as the thiol-ene click reaction between abundant sulfhydryl groups of keratin and the unsaturated double bond of 3-methacryloxy propyltrimethoxy silane (MPTS), and the amino-epoxy reaction between amino groups of keratin and the epoxy group in (3-glycidoxymethyl) methyldiethoxysilane (GPTMS) molecule, along with introduction of PCL as a reinforcing agent. The success of the thiol-ene reaction was verified by the FTIR and 1H-NMR analyses. And the structure of keratin-BG and PCL-keratin-BG composite scaffolds were studied and compared by the FTIR and XRD characterization, which indicated the successful preparation of the PCL-keratin-BG composite scaffold. In addition, the SEM observation, and contact angle and water absorption rate measurements demonstrated that the PCL-keratin-BG composite scaffold has interconnected porous structure, appropriate pore size and good hydrophilicity, which is helpful to cell adhesion, differentiation and proliferation. Importantly, compression experiments showed that, when compared with the keratin-BG composite scaffold, the PCL-keratin-BG composite scaffold increased greatly from 0.91 ± 0.06 MPa and 7.25 ± 1.7 MPa to 1.58 ± 0.21 MPa and 14.14 ± 1.95 MPa, respectively, which suggesting the strong reinforcement of polycaprolactone. In addition, the biomineralization experiment and MTT assay indicated that the PCL-keratin-BG scaffold has good mineralization ability and no-cytotoxicity, which can promote cell adhesion, proliferation and growth. Therefore, the results suggested that the PCL-keratin-BG composite scaffold has the potential as a candidate for application in bone regeneration field. Graphical Abstract

This research aims to improve erosion control practice in the Loess Plateau, by studying the surface erosion processes, including splash, sheet/interrill and rill erosion in four contrasting soils under high rainfall intensity (120 mm h−1) with three-scale indoor artificial experiments. Four contrasting soils as sandy loam, sandy clay loam, clay loam and loamy clay were collected from different parts of the Loess Plateau. The results showed that sediment load was significantly impacted by soil properties in all three sub-processes. Splash rate (4.0–21.6 g m−2∙min−1) was highest in sandy loam from the north part of the Loess Plateau and showed a negative power relation with the mean weight diameter of aggregates after 20 min of rainfall duration. The average sediment load by sheet/interrill erosion (6.94–42.86 g m−2∙min−1) was highest in clay loam from middle part of the Loess Plateau, and the stable sediment load after 20 min showed a positive power relation with the silt content in soil. The average sediment load increased dramatically by rill and interrill erosion (21.03–432.16 g m−2∙min−1), which was highest in loamy clay from south part of the Loess Plateau. The average sediment load after the occurrence of rill showed a positive power relation with clay content and a negative power relation with soil organic matter content. The impacts of slope gradient on the runoff rate and sediment load also changed with soil properties. The critical factors varied for different processes, which were the aggregate size for splash erosion, the content of silt particles and slope gradient for sheet/interrill erosion, and the content of clay particles, soil organic matter and slope gradient for rill erosion. Based on the results of the experiments, specific erosion control practices were proposed by targeting certain erosion processes in areas with different soil texture and different distribution of slope gradient. The findings from this study should support the improvement of erosion prediction and cropland management in different regions of the Loess Plateau.

Background This study was conducted to characterize the long-term effect of mobile-based education on Chinese female freshmen and disclose the possible predictors of their willingness to get vaccinated based on the information-motivation-behavioral skills (IMB) model. Methods We randomly assigned 509 participants to a 7-day mobile-based educational intervention or control group and collected information about general information, health, and sexual behavior, HPV vaccination intention and action, HPV-related knowledge, cognition, and behavioral skill by an online self-administrated questionnaire at baseline, post-intervention, and at the 1-month and 3-month follow-ups. Results The intervention arm showed an improvement in IMB scores after education. Despite the persistent improvement in knowledge, the improvement in their motivation and behavioral skills decreased at the 1-month and 3-month follow-ups. Participants’ vaccination willingness was elevated after the baseline survey in both the intervention and control groups, while the overall appointment/vaccination rate was only 3.73% 3 months later. The intention to get vaccinated was associated with knowing HPV (adjusted OR: 2.37, 95% CI: 1.44 – 3.89), perceiving more barriers (adjusted OR: 2.16, 95% CI: 1.44 – 3.25), higher subjective norms (adjusted OR: 2.05, 95% CI: 1.26 – 3.32), and having more behavioral skills (adjusted OR: 2.95, 95% CI: 1.79 – 4.87). Conclusion Seven-day mobile-based education was effective to increase IMB model scores among female freshmen. However, the improvement in motivation and behavioral skills was not persistent. Information, perceived barriers, subjective norms, and behavioral skills were discovered to be influencing factors of vaccination intention. Future research with longer, more convenient, and more tailored education to the main influencing factors is warranted.

Abstract Silicic acid, commonly derived from cheap and easily available sodium silicate, has recently received great attention for application in leather industry to produce ecological leather with a cleaner approach. However, leather tanned with silicic acid alone is poor in storage stability, which limits its practical application in leather production. In this work, a new environment-friendly combination tannage based on silicic acid and plant tannin was developed to address this issue along with improving the comprehensive performances of leather. The obtained leather was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and so on. The results showed that compared with leather tanned with silicic acid alone, the leather tanned with this combination method possessed improved thermal stability, enhanced mechanical properties, acceptable softness, appropriate hydrophilicity, and especially enhanced storage stability. More importantly, the combination tanned leather with 1:1 of the mass ratio of silicic acid to vegetable tannin (composed of valonea extract and mimosa extract with the same weight) had more prominent comprehensive performances. In addition, the results demonstrated that hydrogen bonding played an important role in the combination tanning process. Furthermore, the hydrogen bonds generated between phenolic hydroxyl groups of polyphenols with silicon hydroxyl groups of silicic acid molecules inhibited the excessive condensation of Si-OH groups between themselves. Subsequently, the assessment of environmental impact revealed the value of BOD5/COD of the wastewater produced in this combination tanning process is more than 0.3, indicating the chrome-free combination tannage based on silicic acid and plant tannin was an environment-friendly tanning technology. These findings therefore indicated that a new chrome-free tanning method with silicon and biomass materials as main tanning agents has potential practical application prospect in leather production. Graphical abstract

BackgroundActin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers.MethodsThe public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan–Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman’s correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells.ResultsARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint–related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells.ConclusionsARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.

Disorders of sexual development (DSD) refer to the congenital abnormalities of chromosomes, gonads, or gender anatomy. Children with DSD usually experience more stress. The present study aims to evaluate the mental health status of children with DSD, and to explore the potential relevant factors. We included 30 children with DSD and 30 age- and gender-matched children without DSD as the control group. All the children and their parents completed the scales of the Hamilton Anxiety Scale (HAMA). Children over 8 years old (n = 22) completed the Screen Scale for Child Anxiety Related Emotional Disorders (SCARED), the Depression Self-rating Scale for Children (DSRSC), and the Egna Minnen av Barndoms Uppfostran-own memories of parental rearing practices in childhood. DSD children had significantly higher somatic anxiety, mental anxiety, and total anxiety scores than the control group (p < 0.001). The scores of the SCARED, anxiety, and depression subscales of DSD children were higher than those of control children (p < 0.05 and p < 0.001, respectively). The correlation analysis showed that the score of generalized anxiety was positively related to age and entertainment. The regression analysis showed that age was a major factor that affected generalized anxiety in DSD children, and neuroticism was a major factor of anxiety disorder and separation anxiety in DSD children. Children with DSD have obvious anxiety problems, which are associated with family environmental factors (entertainment, success, and conflicts) and age. It is important to focus emphasis on emotional stability in children with DSD for detecting anxiety-related emotional disorders early.

Congenital limb malformations (CLMs) affect 1 in 500 live births. However, the value of exome sequencing (ES) for CLM is lacking. The purpose of this study was to decipher the mutational signature of CLM on an exome level. We enrolled a cohort of 66 unrelated probands (including 47 families) with CLM requiring surgical correction. ES was performed for all patients and available parental samples. A definite molecular diagnosis was achieved in 21 out of 66 (32%) patients. We identified 19 pathogenic or likely pathogenic single-nucleotide variants and three copy number variants, of which 11 variants were novel. We identified four variants of uncertain significance. Additionally, we identified RPL9 and UBA2 as novel candidate genes for CLM. By comparing the detailed phenotypic features, we expand the phenotypic spectrum of diastrophic dysplasia and chromosome 6q terminal deletion syndrome. We also found that the diagnostic rate was significantly higher in patients with a family history of CLM (p = 0.012) or more than one limb affected (p = 0.034). Our study expands our understanding of the mutational and phenotypic spectrum of CLM and provides novel insights into the genetic basis of these syndromes.

Abstract Background Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery. Methods The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model. Results In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59–0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54–0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68–0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (

Objective To evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhotic PVT, and compare differences in efficacy and safety among different anticoagulants. Methods We comprehensively searched Pubmed, Cochrane Library, EMBASE, and ClinicalTrials.gov from inception to April 2022 for studies using anticoagulants for cirrhotic PVT. Meta-analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results 3 RCTs and 14 cohort studies involving 1270 patients were included. Anticoagulant therapy can increase the recanalization rate compared with non-anticoagulation therapy (OR 4.44, 95% CI 3.11-6.32, I 2 = 2.5%) and can decrease the extension rate of cirrhotic PVT (OR 0.33, 95% CI 0.18-0.62, I 2 = 41.0%), without increasing the incidence of total bleeding (OR 1.21, 95% CI 0.75-1.97, I 2 = 9.8%), major bleeding (OR 0.98, 95% CI 0.49-1.95, I 2 = 19.7%), and variceal bleeding (OR 0.35, 95% CI 0.12-1.01, I 2 = 39.9%). Subgroup analysis showed that VKA, LMWH, and DOACs could increase the recanalization rate of PVT and were not associated with the risk of bleeding. Studies that compared direct oral anticoagulants (DOACs) with warfarin directly showed that the recanalization rate of PVT in the DOACs group might be higher than that in the warfarin group (OR 30.99, 95% CI 7.39-129.87, I 2 = 0.0%), and there was no difference in the rate of total bleeding (OR 0.30, 95% CI 0.01-8.65, I 2 = 79.6%). Conclusions Anticoagulants are safe and effective in patients with cirrhotic PVT. The rate of PVT recanalization associated with DOACs may be higher than warfarin.

Boronization is an important wall conditioning procedure for realizing the steady-state high performance operation of tokamaks such as KSTAR and ITER. The measurement of boron and its distribution on the first wall and divertor has a significant impact on studying the plasma-wall interaction (PWI) such as impurity generation, transportation and deposition behaviors. In this study, the laser-induced breakdown spectroscopic (LIBS) diagnostic method was applied in the lab for investigating the boron impurity deposited on the surface of different shaped tungsten (W) castellated tiles which were removed from the divertor region in the Korea Superconducting Tokamak Advanced Research (KSTAR). Meanwhile, other various impurity elements comprising carbon, silicon, calcium and copper were also observed. A subtraction method is proposed to eliminate the W line contribution for B deposition measurement. The depth profile of the impurity elements in the deposited layer also has been studied by the variation of spectral intensity with consecutive laser pulses. The lateral-distribution of the boron and carbon on the three tungsten castellated tiles (Rounded, Chamfered and Double chamfered) were carried out at 10−5 mbar vacuum condition. The distribution features of the impurities on the three different shaped tungsten tiles provide valuable information to understand PWI process in KSTAR. This study demonstrates that LIBS is a potential diagnostic approach for monitoring the impurity deposition in tokamak such as KSTAR or ITER.

Cerebral small vessel disease (CSVD) is often referred to as “collaterals disease” in traditional Chinese medicine (TCM), and commonly includes ischemic and hemorrhagic CSVD. TCM has a long history of treating CSVD and has demonstrated unique efficacy. Buyang Huanwu Decoction (BHD) is a classical TCM formula that has been used for the prevention and treatment of stroke for hundreds of years. BHD exerts its therapeutic effects on CSVD through a variety of mechanisms. In this review, the clinical and animal studies on BHD and CSVD were systematically introduced. In addition, the pharmacological mechanisms, active components, and clinical applications of BHD in the treatment of CSVD were reviewed. We believe that an in-depth understanding of BHD, its pharmacological mechanism, disease-drug interaction, and other aspects will help in laying the foundation for its development as a new therapeutic strategy for the treatment of CSVD.

BackgroundRecurrent urinary tract infection (RUTI) is common and burdensome in women. Due to the low concentration or slow-growing of uropathogens in RUTI, standard urine cultures (SUCs) are often negative. Next-generation sequencing (NGS) of bacterial 16S rRNA gene is more sensitive and could be used to reveal the differential microbiota between patients with RUTI and asymptomatic controls.MethodsWomen (aged ≥ 18 years) with clinically diagnosed RUTI with negative SUC and age-matched women asymptomatic controls with normal urinalysis were enrolled. Their midstream voided urine specimens were collected and processed for NGS (Illumina MiSeq) targeting the bacterial 16S rRNA gene V3-V4 region. The dataset was clustered into operational taxonomic units (OTUs) using QIIME. Taxonomic analysis, alpha diversity, beta diversity, multivariate statistical analysis, and linear discriminant analysis effect size (LEfSe) for differential analysis were performed and compared between patients with RUTI and asymptomatic controls.ResultsA total of 90 patients with RUTI and 62 asymptomatic controls were enrolled in this study. Among them, 74.4% (67/90) and 71.0% (44/62) were successfully amplified and sequenced their bacterial 16S rRNA gene. In the alpha diversity analysis, the chao1 index and observed species index were significantly lower in the RUTI group than in the control group (P = 0.015 and 0.028, respectively). In the beta diversity analysis, there was a significant difference between the 2 groups [Analysis of similarities (ANOSIM), R = 0.209, P = 0.001]. The relative abundance of 36 bacterial taxa was significantly higher, and another 24 kinds of bacteria were significantly lower in the RUTI group compared with the control group [LEfSe analysis, P < 0.05, linear discriminative analysis (LDA) score > 3], suggesting that Ralstonia, Prevotella, Dialister, and Corynebacterium may play an important role in RUTI.ConclusionThe urinary microbiota of women with clinically diagnosed RUTI were significantly different from age-matched asymptomatic controls.

ABSTRACT: Background: Acute Achilles tendon rupture is a severe injury of the lower extremities; however, optimal treatment options are not yet available. This study aimed to investigate the surgical method and clinical effect of the Krackow and tendon-bundle techniques for managing acute Achilles tendon rupture. Methods: This retrospective case series study analyzed 17 cases of acute Achilles tendon rupture at the Beijing Jishuitan Hospital from December 2012 to January 2020. There were 16 men and one woman, aged 27–45 years, with an average of 39.6 years. Thirteen patients were injured while playing basketball or badminton, and 4 patients were injured while participating in a football match or other sports. All injuries were repaired using the Krackow and tendon-bundle techniques. Postoperative evaluation indicators included active range of motion during ankle plantar flexion and dorsiflexion, height of single foot heel lifting, Amer-Lindholm Achilles tendon function score, and American Orthopedic Foot and Ankle Society (AOFAS) score. Results: The patients were followed-up for 6–45 months (average, 18.9 months). There was no re-rupture of the Achilles tendon, wound infection, or sural nerve injury. At the final follow-up, the affected and contralateral sides exhibited plantar flexion of 42.1 ± 4.4 ° and 43.8 ± 2.8 °, dorsiflexion of 15.8 ± 2.9 ° and 16.6 ± 2.9 °, respectively, and one foot exhibited a heel lifting height of 7.2 ± 1.0 cm and 7.5 ± 0.9 cm, respectively. There was no significant difference between the affected and contralateral sides (P>0.05). At the final follow-up, the Amer-Lindholm Achilles tendon function score was excellent in 94.1% (16/17) of the patients and good in 5.9% (1/17) of the patients. The AOFAS scores ranged from 90 to 100, with an average of 96.4 ± 3.7. Conclusion: Krackow and tendon-bundle techniques can improve the strength of the suture used for the Achilles tendon repair and ensure good matching for broken ends, and thus it is an effective repair method for closed Achilles tendon injury.