Efficacy and Safety Analysis of Transarterial Chemoembolization Plus Donafenib With or Without Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Prospective, Single-Arm, Single-Center, Phase II Clinical Study.

Purpose: To observe and assess the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) to treat unresectable hepatocellular carcinoma (HCC). Patients and Methods: This prospective, single-arm, single-center, phase II clinical study enrolled 36 patients with initial unresectable HCC who had not undergone any systemic treatment. The patients received donafenib plus TACE (n = 26) or donafenib plus TACE plus programmed death receptor 1 inhibitors (n = 10). The primary endpoint was short-term efficacy, with secondary endpoints including progression-free survival (PFS), time to response (TTR), disease control rate (DCR), and adverse events. The tumor feeding artery diameter was also measured. Results: Efficacy evaluation of all 36 patients revealed 6 cases of complete response, 19 of partial response, 8 of stable disease, and 3 of progressive disease. Six (16.7%) patients successfully underwent conversion surgery, all achieving R0 resection, and 2 (5.6%) achieved a complete pathological response. The objective response rate (ORR) was 69.4% and the DCR was 91.7%. The median PFS was 10.7 months, the median overall survival was not reached, and the median TTR was 1.4 months. The median survival rates at 6, 12, and 18 months were 85.0%, 77.6%, and 71.3%, respectively. The median PFS rates at 6, 12, and 18 months were 65.3%, 45.6%, and 34.2%, respectively. Treatment-related adverse events (TRAEs) occurred in all 25 subjects, including 4 (11.3%) grade 3 TRAEs. No grade 4 or 5 TRAEs occurred. The tumor feeding artery diameter was significantly decreased following treatment (P = 0.036). Multivariable analysis revealed the sum of baseline target lesion diameters, best tumor response, and combined immunotherapy as independent predictors of PFS. Conclusion: TACE plus donafenib reduced the tumor feeding artery diameter in patients with unresectable HCC. The safety profile was good, and a high ORR was achieved.

Inappropriate use of antibiotic enhances antibiotic resistance dissemination in ESBL-EC: Role of ydcz in outer membrane vesicles biogenesis and protein transport.

Extended-spectrumß-lactam producing Escherichia coli (ESBL-EC) readily colonizes live poultry and serves as a major source of contamination in retail chicken meat, posing significant threats to public health. This study aims to investigate the impact of inappropriate antibiotic use on the dissemination and exacerbation of antibiotic resistance in ESBL-EC and explore the underlying molecular mechanisms. Through experimental analysis, we propose a hypothesis that inappropriate antibiotic use may exacerbate resistance by affecting vesicle formation and protein secretion. Experimental results demonstrate that under the influence of amoxicillin, the concentration of proteins secreted in outer membrane vehicles (OMVs) by ESBL-EC significantly increases, along with a significant upregulation in the expression of the CTX-M-55-type Extended-spectrum beta-lactamase (CTX-M-55). Proteomic analysis and differential gene knockout experiments identified the key protein YdcZ, associated with OMVs formation and protein transportation in ESBL-EC under amoxicillin treatment. Further investigations reveal direct interactions between YdcZ and other proteins (YdiH and BssR). Upon ydcz gene knockout, a significant decrease in protein concentration within OMVs is observed, accompanied by a noticeable reduction in protection against sensitive bacteria. These findings suggest a critical role of YdcZ in regulating the process of protein transportation to OMVs in ESBL-EC under the influence of amoxicillin. In summary, our research uncovers the significant role of inappropriate antibiotic use in promoting the secretion of OMVs by ESBL-EC, aiding the survival of antibiotic-sensitive bacteria in the vicinity of infection sites. These findings provide new insights into the mechanisms underlying antibiotic-induced bacterial resistance dissemination and offer novel avenues for exploring prevention and control strategies against bacterial resistance propagation.

Development and validation of matrix metalloproteinase for predicting prognosis and tumour microenvironment immune profiles in uterine corpus endometrial carcinoma.

Background: Matrix metalloproteinases (MMPs) are involved in many processes of tumour progression and invasion. However, few studies have analysed the effects of MMP expression patterns on endometrial cancer (EC) development from the perspective of the tumour microenvironment (TME). we quantified MMP expression in individual by constructing an MMP score and found MMP score effectively predict the prognosis of EC patients. Methods: MMPs expression profiles were determined based on the differential expression of 12 MMP-related regulators. Principal component analysis (PCA) was used to construct an MMP scoring system which can quantify the MMPs expression patterns individually of EC patients. Kaplan-Meier analysis, the log-rank test, and time-dependent receiver operating characteristic (ROC) curve analysis were used to evaluate the value of MMPs expression in predicting prognosis. Single-cell RNA sequencing (scRNA-seq) dataset was used to verify correlation between MMPs and progression of EC. Gene Ontology (GO) analysis was used to investigate the pathways and functions underlying MMPs expression. Tumour immune dysfunction, exclusion prediction, and pharmacotherapy response analyses were performed to assess the potential response to pharmacotherapy based on MMPs patterns. Results: We downloaded the MMPs expression data, somatic mutation data and corresponding clinical information of EC patients from the TCGA website and ICGC portal. Based on the MMP-related differentially expressed genes (DEGs), the MMP score was constructed, and EC patients were divided into high and low MMP score groups. There was a positive correlation between MMP score and prognosis of EC patients. Patients with high MMP scores had better prognosis, more abundant immune cell infiltration and stronger antitumoor immunity. Although prognosis is worse with the lower group than the high, patients with low MMP score had better response to immunotherapy, which means they could prolong the survival time through Immunological checkpoint blockade (ICB) therapy. scRNA-seq analysis identified significant heterogeneity between MMP score and classical pathways in EC. Conclusion: Our work indicates that the MMP score could be a potential tool to evaluate MMP expression patterns, immune cell infiltration, response to pharmacotherapy, clinicopathological features, and survival outcomes in EC. This will provide the more effective guide to select immunotherapeutic strategies of EC in the future.

Enhancing Mechanical and Antimicrobial Properties of Dialdehyde Cellulose-Silver Nanoparticle Composites through Ammoniated Nanocellulose Modification.

Given the widespread prevalence of viruses, there is an escalating demand for antimicrobial composites. Although the composite of dialdehyde cellulose and silver nanoparticles (DAC@Ag1) exhibits excellent antibacterial properties, its weak mechanical characteristics hinder its practical applicability. To address this limitation, cellulose nanofibers (CNFs) were initially ammoniated to yield N-CNF, which was subsequently incorporated into DAC@Ag1 as an enhancer, forming DAC@Ag1/N-CNF. We systematically investigated the optimal amount of N-CNF and characterized the DAC@Ag1/N-CNF using FT-IR, XPS, and XRD analyses to evaluate its additional properties. Notably, the optimal mass ratio of N-CNF to DAC@Ag1 was found to be 5:5, resulting in a substantial enhancement in mechanical properties, with a 139.8% increase in tensile elongation and a 33.1% increase in strength, reaching 10% and 125.24 MPa, respectively, compared to DAC@Ag1 alone. Furthermore, the inhibition zones against Escherichia coli and Staphylococcus aureus were significantly expanded to 7.9 mm and 15.9 mm, respectively, surpassing those of DAC@Ag1 alone by 154.8% and 467.9%, indicating remarkable improvements in antimicrobial efficacy. Mechanism analysis highlighted synergistic effects from chemical covalent bonding and hydrogen bonding in the DAC@Ag1/N-CNF, enhancing the mechanical and antimicrobial properties significantly. The addition of N-CNF markedly augmented the properties of the composite film, thereby facilitating its broader application in the antimicrobial field.

Freeprotmap: waiting-free prediction method for protein distance map.

BACKGROUND: Protein residue-residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue-residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. RESULT: In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue-residue distances in tens of milliseconds and has higher precision than the best structure prediction method. CONCLUSION: Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue-residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.

pDenoiser: A Personalized Speech Enhancement Neural Network for Pre-hospital Emergency Medical Services.

Pre-hospital emergency medical service (EMS) tasks often come with complex and diverse noise interferences, posing challenges in implementing ASR-based medical technologies and hindering efficient and accurate telephonic communication. Among the different types of noise distortion, interfering speech is especially annoying. To address these issues, our aim is to develop a technology capable of extracting the intended speech content of the target physician from noisy and mixed audio during EMS tasks. In this work, we propose a monoaural personalized speech enhancement (PSE) method called pDenoiser, which is a real-time neural network that operates in the time domain. By leveraging the prior vocalization cues of emergency physicians, pDenoiser selectively enhances target speech components while suppressing noise and nontarget speech components, thereby improving speech quality and speech recognition accuracy under noisy conditions. We demonstrate the potential value of our approach through evaluations on both public general-domain test sets and our self-collected real-world EMS test sets. The experimental results are promising, as our model effectively promotes both speech quality and ASR performance under various conditions and outperforms related methods across multiple evaluation metrics. Our methodology will hopefully elevate EMS efficiency and fortify security against nontarget speech during EMS tasks.

Leveraging existing 16S rRNA gene surveys to decipher microbial signatures and dysbiosis in cervical carcinogenesis.

The presence of dysbiotic cervicovaginal microbiota has been observed to be linked to the persistent development of cervical carcinogenesis mediated by the human papillomavirus (HPV). Nevertheless, the characteristics of the cervical microbiome in individuals diagnosed with cervical cancer (CC) are still not well understood. Comprehensive analysis was conducted by re-analyzing the cervical 16S rRNA sequencing datasets of a total of 507 samples from six previously published studies. We observed significant alpha and beta diversity differences in between CC, cervical intraepithelial neoplasia (CIN) and normal controls (NC), but not between HPV and NC in the combined dataset. Meta-analysis revealed that opportunistic pernicious microbes Streptococcus, Fusobacterium, Pseudomonas and Anaerococcus were enriched in CC, while Lactobacillus was depleted compared to NC. Members of Gardnerella, Sneathia, Pseudomonas, and Fannyhessea have significantly increased relative abundance compared to other bacteria in the CIN group. Five newly identified bacterial genera were found to differentiate CC from NC, with an area under the curve (AUC) of 0.8947. Moreover, co-occurrence network analysis showed that the most commonly encountered Lactobacillus was strongly negatively correlated with Prevotella. Overall, our study identified a set of potential biomarkers for CC from samples across different geographic regions. Our meta-analysis provided significant insights into the characteristics of dysbiotic cervicovaginal microbiota undergoing CC, which may lead to the development of noninvasive CC diagnostic tools and therapeutic interventions.

Tackling Antibiotic Resistance: Exploring 5-Fluorouracil as a Promising Antimicrobial Strategy for the Treatment of Streptococcus suis Infection.

Streptococcus suis (S. suis) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis, are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics.

Water-soluble silver nanoclusters with multicolor fluorescence generated by dialdehyde nanofibrillated cellulose for biological imaging.

Water-soluble silver nanoclusters (AgNCs) as a new type of fluorescent material have attracted much attention for their remarkable optical properties and excellent cytocompatibility. However, it is still challenging to synthesize water-soluble AgNCs with good cytocompatibility and excellent fluorescence. Herein, the dialdehyde nanofibrillated cellulose (DANFC)- reduced water-soluble AgNCs capped by glutathione (GSH) with tunable fluorescence emissions were first reported. The DANFC provides a mild reduction environment and crystal growth system for the coordination between silver ions and GSH compared to conventional methods using strong reducing agents. The AgNCs with intense red fluorescence (R-AgNCs@GSH, size ∼2.24 nm) and green fluorescence (G-AgNCs@GSH, size ∼1.93 nm) were produced by varying the ratios of silver sources and ligands, and could maintain stable fluorescence intensity over 6 months. Moreover, the CCK-8 study demonstrated that the R-AgNCs@GSH and G-AgNCs@GSH reduced by DANFC of excellent cytocompatibility (cell viability >90 %) and enable precise multicolor intracellular imaging of Hela cells in 1 h. This work proposes a novel method to synthesize water-soluble AgNCs with tunable fluorescence emission at room temperature based on the classical silver- mirror reaction (SMR) using DANFC as reducing agent, and the synthesized fluorescent AgNCs have great potential as novel luminescent nanomaterials in biological research.

Mendelian randomization reveals association of gut microbiota with Henoch-Schönlein purpura and immune thrombocytopenia.

Gut microbiota have been linked to immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) in recent studies, but a cause-and-effect relationship is unclear. We used Mendelian randomization (MR) to assess causal relationships between gut microbiota and HSP/ITP using summary statistics from the GWAS dataset of the international MiBioGen and FinnGen consortium. The IVW method was used as the main evaluation indicator. MR analysis of 196 intestinal flora and HSP/ITP/sTP phenotypes showed that 12 flora were potentially causally associated with ITP, 6 with HSP, and 9 with sTP. The genes predicted that genus Coprococcus3 (p = 0.0264, OR = 2.05, 95% CI 1.09-3.88)and genus Gordonibacter (p = 0.0073, OR = 1.38; 95% CI 1.09-1.75) were linked to a higher likelihood of developing ITP. Additionally, family Actinomycetaceae (p = 0.02, OR = 0.51, 95% CI 0.28-0.90) and order Actinomycetales (p = 0.0199, OR = 0.50, 95% CI 0.28-0.90) linked to reduced HSP risk. Genus Ruminococcaceae UCG013 (p = 0.0426, OR = 0.44, 95% CI 0.20-0.97) negatively correlated with sTP risk. Our MR analyses offer evidence of a possible cause-and-effect connection between certain gut microbiota species and the likelihood of HSP/ITP.

The potassium transporter TaNHX2 interacts with TaGAD1 to promote drought tolerance via modulating stomatal aperture in wheat.

Drought is a major global challenge in agriculture that decreases crop production. γ-Aminobutyric acid (GABA) interfaces with drought stress in plants; however, a mechanistic understanding of the interaction between GABA accumulation and drought response remains to be established. Here we showed the potassium/proton exchanger TaNHX2 functions as a positive regulator in drought resistance in wheat by mediating cross-talk between the stomatal aperture and GABA accumulation. TaNHX2 interacted with glutamate decarboxylase TaGAD1, a key enzyme that synthesizes GABA from glutamate. Furthermore, TaNHX2 targeted the C-terminal auto-inhibitory domain of TaGAD1, enhanced its activity, and promoted GABA accumulation under drought stress. Consistent with this, the tanhx2 and tagad1 mutants showed reduced drought tolerance, and transgenic wheat with enhanced TaNHX2 expression had a yield advantage under water deficit without growth penalty. These results shed light on the plant stomatal movement mechanism under drought stress and the TaNHX2-TaGAD1 module may be harnessed for amelioration of negative environmental effects in wheat as well as other crops.

Methyltransferase TaSAMT1 mediates wheat freezing tolerance by integrating brassinosteroid and salicylic acid signaling.

Cold injury is a major environmental stress affecting the growth and yield of crops. Brassinosteroids (BRs) and salicylic acid (SA) play important roles in plant cold tolerance. However, whether or how BR signaling interacts with the SA signaling pathway in response to cold stress is still unknown. Here, we identified an SA methyltransferase, TaSAMT1, that converts SA to methyl SA (MeSA) and confers freezing tolerance in wheat (Triticum aestivum). TaSAMT1 overexpression greatly enhanced wheat freezing tolerance, with plants accumulating more MeSA and less SA, whereas Tasamt1 knockout lines were sensitive to freezing stress and accumulated less MeSA and more SA. Spraying plants with MeSA conferred freezing tolerance to Tasamt1 mutants, but SA did not. We revealed that BRASSINAZOLE-RESISTANT 1 (TaBZR1) directly binds to the TaSAMT1 promoter and induces its transcription. Moreover, TaBZR1 interacts with the histone acetyltransferase TaHAG1, which potentiates TaSAMT1 expression via increased histone acetylation and modulates the SA pathway during freezing stress. Additionally, overexpression of TaBZR1 or TaHAG1 altered TaSAMT1 expression and improved freezing tolerance. Our results demonstrate a key regulatory node that connects the BR and SA pathways in the plant cold stress response. The regulatory factors or genes identified could be effective targets for the genetic improvement of freezing tolerance in crops.

Characteristics of lymphocyte subsets and inflammatory factors in patients with COVID-19.

Objective: This research aims to examine the involvement of lymphocyte subsets and inflammatory cytokines in the development and progression of COVID-19. Methods: 164 COVID-19 patients were admitted to hospital between December 2022 and January 2023. Based on lung CT scans and whether it is necessary for intensive care unit (ICU) admission, they were categorized into: severe groups (84) and mild disease groups (80). Peripheral blood were also collected from 101 healthy examinees and 164 patients. Flow cytometry (FCM) was used to measure the absolute and relative counts of lymphocyte subsets, while chemiluminescence was used to detect the level of inflammatory cytokines. Results: The COVID-19 patient group exhibited lower count of lymphocytes subsets than healthy control group. Moreover, COVID-19 patient case presented higher content of cytokines (IL-6, IL-4, IL-8, IL-10, and TNF-α) expression compared to healthy control case. Within the COVID-19 patient group, individuals with severe disease showed lower counts of lymphocytes subsets than the mild disease case. Furthermore, IL-6 levels in severe case were higher than the mild disease patients case. Multi-variate logistic regression analysis confirmed IL-6 (odds ratio: 0.985 [0.977-0.993]), CD3+ T cells (odds ratio:1.007 [1.004-1.010]), CD8+ T cells (odds ratio:1.016 [1.009-1.023]), and CD19+ B cells (odds ratio:1.011 [1.002-1.020]) independently predicted severe progression. ROC curve results indicated AUC for lymphocytes in patients with severe COVID-19 was 0.8686 (0.8112-0.9260), CD3+ T cells was 0.8762 (0.8237-0.9287), CD8+ T cells was 0.7963 (0.7287-0.8638), CD4+ T cells was 0.8600 (0.8036-0.9164), CD19+ B cells was 0.7217 (0.6434-0.8001), NK cells was 0.6492 (0.5627-0.7357), age was 0.6699 (0.5877-0.7521), diabetes was 0.5991 (0.5125-0.6857), and IL-6 was 0.7241 (0.6479-0.8003). Furthermore, the ROC curves for different factors (CD3+ T cells, age, IL-6) yielded an AUC of 0.9031 (0.8580-0.9483). Conclusions: The research indicated that COVID-19 patients experience a decrease in lymphocytes subset and an increase in the inflammatory factor IL-6, particularly in the severe case group. As a result, the count of lymphocyte subset (CD3+ T cells) and the content of inflammatory cytokine (IL-6) can serve as predictive markers for assessing the severity of COVID-19 and developing treatment plans efficacy.

ESBL-Escherichia coli extracellular vesicles mediate bacterial resistance to ß-lactam and mediate horizontal transfer of blaCTX-M-55.

OBJECTIVES: Extracellular vesicles (EVs) have become the focus of research as an emerging method of horizontal gene transfer. In recent years, studies on the association between EVs and the spread of bacterial resistance have emerged, but there is a lack of research on the role of EVs secreted by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli in the spread of ß-lactam resistance. Therefore, the aim of this study was to investigate the role of EVs in the transmission of ß-lactam resistance. METHODS: In this study, the role of EVs in the transmission of ß-lactam resistance in E. coli was evaluated by the EVs-mediated bacterial resistance to ß-lactam antibiotics test and the EVs-mediated blaCTX-M-55 transfer experiments using EVs secreted by ESBL-E. coli. RESULTS: The results showed that ESBL-EVs were protective against ß-lactam antibiotic-susceptible bacteria, and this protective effect was dependent on the integrity of the EVs and showed dose- and time-dependent effects. At the same time, ESBL-EVs can also mediate the horizontal transmission of blaCTX-M-55, and EVs-mediated gene transfer is selective, preferring to transfer in more closely related species. CONCLUSIONS: In this study, we demonstrated the important role of EVs in the transmission of ß-lactam resistance in chicken ESBL-E. coli, and evaluated the risk of EVs-mediated horizontal gene transfer, which provided a theoretical basis for elucidating the mechanism of EVs-mediated resistance transmission.

Skin healthcare protection with antioxidant and anti-melanogenesis activity of polysaccharide purification from Bletilla striata.

In this study, we investigated the structural characterization and biological activities of Bletilla striata polysaccharides (BSPs) for their role as antioxidants and anti-melanogenesis agents in skin healthcare protection. Three neutral polysaccharides (BSP-1, BSP-2, and BSP-3) with molecular weights of 269.121 kDa, 57.389 kDa, and 28.153 kDa were extracted and purified. Their structural characteristics were analyzed by ion chromatography, GC-MS, and 1D/2D NMR. The results showed that BSP-1, which constitutes the major part of BSPs, was composed of α-D-Glcp, ß-D-Glcp, ß-D-Manp, and 2-O-acetyl-ß-D-Manp, with the branched-chain accompanied by ß-D-Galp and α-D-Glcp. BSP-1, BSP-2, and BSP-3 can enhance the total antioxidant capacity of skin fibroblasts with non-toxicity. Meanwhile, BSP-1, BSP-2, and BSP-3 could significantly inhibit the proliferative activity of melanoma cells. Among them, BSP-1 and BSP-2 showed more significance in anti-melanogenesis, tyrosinase inhibition activity, and cell migration inhibition. BSPs have effective antioxidant capacity and anti-melanogenesis effects, which should be further emphasized and developed as skin protection components.

Performance and Interfacial Microstructure of Al/Steel Joints Welded by Resistance Element Welding.

In this study, an upper sheet of an A6061 aluminum alloy and a lower sheet of Q235 steel were welded by resistance element welding with a steel rivet. The temperature field during welding was calculated using ABAQUS numerical simulation software, and the interfacial microstructure was observed. A nugget was formed between the rivet shank and the lower sheet. With increases in welding current and welding time, the tensile shear load of the joint increased first and then decreased slightly. When the welding current was 14 kA and the welding time was 300 ms, the tensile shear load of the joint reached a maximum of 7.93 kN. The smaller the distance from the position to the lower sheet along the interface between the rivet shank and upper sheet, the longer the high-temperature duration and the higher the peak temperature during welding. At the junction of the rivet shank, upper sheet, and lower sheet in the joint, the high-temperature duration was the longest, at about 392 ms, and the peak temperature was the highest, at about 1237 °C. The results show that the smaller the distance from the position to the lower sheet along the interface between the rivet shank and the upper sheet in the joint, the thicker the reaction layer generated there, and that the thickness of the reaction layer was about 2.0 µm at the junction of the rivet shank, upper sheet, and lower sheet in the joint.

Ultra-strong, nonfreezing, and flexible strain sensors enabled by biomass-based hydrogels through triple dynamic bond design.

Biomass-based hydrogels have displayed excellent potential in flexible strain sensors due to their adequacy, biocompatibility, nontoxic and degradability. Nevertheless, their inferior mechanical properties, particularly at cryogenic temperatures, impeded their extensive utilization. Herein, we reported a rationally designed strain sensor fabricated from a gelatin and cellulose-derived hydrogel with superior mechanical robustness, cryogenic endurance, and flexibility, owing to a triple dynamic bond strategy (TDBS), namely the synergistic reinforcement among potent hydrogen bonds, imine bonds, and sodium bonds. Beyond conventional sacrificing bonds consisting of hydrogen bonds, dynamic covalent bonds and coordinate bonds, synergetic triple dynamic bonds dominated by strong hydrogen bonds and assisted by imine and sodium bonds with higher strength can dissipate more mechanical energy endowing the hydrogel with 38-fold enhancement in tensile strength (6.4 MPa) and 39-fold improvement in toughness (2.9 MPa). We further demonstrated that this hydrogel can work as a robust and biodegradable strain sensor exhibiting remarkable flexibility, broad detection range, considerable sensitivity and excellent sensing stability. Furthermore, owing to the improved nonfreezing performance achieved from incorporating sodium salts, the sensor delivered outstanding sensing properties under subzero conditions such as -20 and -4 °C. It is anticipated that the TDBS can create diverse high-performance soft-electronics for broad applications in human-machine interfaces, energy and healthcare.

A quantitative evaluation of the deep learning model of segmentation and measurement of cervical spine MRI in healthy adults.

PURPOSE: To evaluate the 3D U-Net model for automatic segmentation and measurement of cervical spine structures using magnetic resonance (MR) images of healthy adults. MATERIALS AND METHODS: MR images of the cervical spine from 160 healthy adults were collected retrospectively. A previously constructed deep-learning model was used to automatically segment anatomical structures. Segmentation and localization results were checked by experienced radiologists. Pearson's correlation analyses were conducted to examine relationships between patient and image parameters. RESULTS: No measurement was significantly correlated with age or sex. The mean values of the areas of the subarachnoid space and spinal cord from the C2/3 (cervical spine 2-3) to C6/7 intervertebral disc levels were 102.85-358.12 mm2 and 53.71-110.32 mm2 , respectively. The ratios of the areas of the spinal cord to the subarachnoid space were 0.25-0.68. The transverse and anterior-posterior diameters of the subarachnoid space were 14.77-26.56 mm and 7.38-17.58 mm, respectively. The transverse and anterior-posterior diameters of the spinal cord were 9.11-16.02 mm and 5.47-10.12 mm, respectively. CONCLUSION: A deep learning model based on 3D U-Net automatically segmented and performed measurements on cervical spine MR images from healthy adults, paving the way for quantitative diagnosis models for spinal cord diseases.

Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in Proteus mirabilis isolated from China, 2018-2020.

Proteus mirabilis can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of P. mirabilis were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive P. mirabilis exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to Escherichia coli EC600 with a frequency of 2.0 × 10-7 to 6.0 × 10-5. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICEPmiChnHBRJC2 carries erm (42), which have never been found within an SXT/R391 ICE in P. mirabilis, and ICEPmiChnSC1111 carries 19 ARGs, including clinically important cfr, blaCTX-M-65, and aac(6')-Ib-cr, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICEPmiChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICEPmiChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in P. mirabilis.IMPORTANCEThe spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in Proteus mirabilis, which can transfer ARGs to other hosts. The study found that all of the P. mirabilis strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.

RPIOSL: construction of the radiation transfer model for rice leaves.

The radiative transfer model of vegetation leaves simulates the transmission mechanism of light inside the vegetation and simulates the reflectivity of blades according to the change law of different components in the process of plant growth. Based on the PIOSL model, this paper combines PIOSL with the structure of rice leaves to construct a radiation transfer model for rice leaves. The parameters of each layer of the RPIOSL model are determined by the Non-dominated Sorting Genetic Algorithm-III. (NSGA-III.) algorithm. The reflectance spectra of 218 rice leaf samples in different periods were simulated using the RPIOSL model. The results show that the mean (RMSE) between the simulated and measured spectra of the constructed RPIOSL model is 0.1074, which is 0.0191 lower than that of the PROSPECT model. Among them, the spectral simulation effect of RPIOSL model in yellow and red light band is the best, and the RMSE at tillering period, jointing period, heading period and grouting period are 0.0584, 0.0576, 0.0724 and 0.0820, respectively. Therefore, the establishment of the RPIOSL model can accurately describe the interaction mechanism between light, which is of great significance for the rapid acquisition of rice growth information and accurate crop management.