Explore the vast range of titles available.

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986–0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening. A deep learning model provides high accuracy in detecting pancreatic lesions in multicenter data, outperforming radiology specialists.

To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.

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

Introduction The α-glucosidase inhibitor acarbose is an efficacious medicine for the treatment and prevention of type 2 diabetes mellitus (T2DM). However, the response of gut microbiota to acarbose is important, as the microbiota may have a critical role in the development of metabolic diseases, and acarbose is metabolized exclusively within the gastrointestinal tract. We explored the changes in the proportion and diversity of gut microbiota before and after treatment with acarbose in patients with prediabetes. Methods We designed a randomized, double-blind, controlled crossover trial in which 52 Chinese patients with prediabetes by an oral glucose tolerance test (OGTT) with a BMI of 18–35 kg/m 2 were randomly allocated to treatment with acarbose or placebo. Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. Results Of the 52 participants who entered the study, 40 (76.9%) completed the protocol. On the basis of the operational taxonomic unit (OTU) profiles, a total of 107 OTUs were significantly altered after acarbose treatment, with 76 (71%) assigned to the order of Clostridiales . Ruminococcaceae (15 OTUs) and Lachnospiraceae (22 OTUs) decreased in response to acarbose, and 48 OTUs increased by 12.8-fold, including Lactobacillaceae (8 of 9 belonging to Lactobacillus ), Ruminococcaceae (6 of 11 belonging to Faecalibacterium ), and Veillonellaceae (8 of 15 belonging to Dialister ). At genera level, five flourished after treatment with acarbose, including Lactobacillus and Dialister , while Butyricicoccus, Phascolarctobacterium , and Ruminococcus were inhibited. Conclusion This study suggests that the benefits of acarbose for T2DM may correlate with the selective modulation of the gut microbiota. Trial Registration Chinese Clinical Trial Register number, ChiCTR-TTRCC-13004112.

Super-enhancers (SEs) typically govern the expression of critical genes in the maintenance of cell identity. Recent advances suggest mitochondrial dysfunction contributes to pulmonary artery smooth muscle cell (PASMC) proliferation and inflammation in pulmonary hypertension (PH). However, the landscape of SEs in hypoxic PASMCs as well as hypoxia-induced target genes associated with SEs controlling the mitochondrial dysfunction remain to be fully characterized. In this study, we depicted the landscape of SE in hypoxic PASMCs by ChIP-seq, Hi-ChIP, and ChIP-qPCR assays and reveal a regulatory SE driven LncRNA, LINC01013. The effect of LINC01013 on proliferation and inflammation of PASMCs was evaluated through EdU incorporation, Western blotting and immunofluorescence. The molecular mechanism of LINC01013 was investigated by the study of RNA pull down and mass spectrometry. We profiled chromosome interactions in epigenetic regulation and identified SE-associated LINC01013 as a key mitochondrial dysfunction mediator in hypoxic PASMCs. The transcription factor CCAAT enhancer binding protein beta (CEBPB) was found to enrichment in LINC01013 SE and promoter, promoting LINC01013 transcription and overexpression in PASMCs under hypoxic conditions. Inhibition of LINC01013 reversed hypoxia-induced glycolysis and oxidative stress injury of PASMCs. Further investigation unveiled that LINC01013, which is partially located in mitochondria and interacted with heat shock protein family A member 9 (HSPA9) to mediate oligomerization of voltage dependent anion channel 1 (VDAC1), thereby leading to increased mitochondrial permeability and dysfunction. These findings demonstrate that SE-associated LINC01013 regulates the proliferation and inflammation of hypoxic PASMCs by orchestrating mitochondrial function, might be a potential therapeutic target for PH.

The purpose of this study was to ensure the compliance and safety of a robot’s movements during interactions with the external environment. This paper proposes a control strategy for learning variable impedance characteristics from multiple sets of demonstration trajectories. This strategy can adapt to the control of different joints by adjusting the parameters of the variable impedance control policy. Firstly, multiple sets of demonstration trajectories are aligned on the time axis using Dynamic Time Warping. Subsequently, the variance obtained through Gaussian Mixture Regression and a variable impedance strategy based on an improved Softplus function are employed to represent the variance as the variable impedance characteristic of the robotic arm, thereby enabling variable impedance control for the robotic arm. The experiments conducted on a self-designed robotic arm demonstrate that, compared to other variable impedance methods, the motion accuracy of the trajectories of joints 1 to 4 improved by 57.23%, 3.66%, 5.36%, and 20.16%, respectively. Additionally, a stiffness-variable segmented generalization method based on Dynamic Movement Primitive is proposed to achieve variable impedance control in various task environments. This strategy fulfills the requirements for compliance and safety during robot interactions.

Abnormal pulmonary arterial smooth muscle cells (PASMCs) proliferation is an important pathological process in hypoxic pulmonary arterial hypertension. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation–apoptosis balance. However, the molecular mechanism is still unknown. We used hypoxic animal models, cell biology, and molecular biology to determine the effect of mitofusin 1 (Mfn1) on hypoxia-mediated PASMCs mitochondrial homeostasis. We found that Mfn1 expression was increased in hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and smooth muscle cell proliferation as well as hypoxia-stimulated cell-cycle transition from the G 0 /G 1 phase to S phase. Subsequently, we studied the role of microRNAs in mitochondrial function associated with PASMC proliferation under hypoxic conditions. The promotive effect of Mfn1 on pulmonary vascular remodeling was alleviated in the presence of miR-125a agomir, and miR-125a antagomir mimicked the hypoxic damage effects to mitochondrial homeostasis. Moreover, in vivo and in vitro treatment with miR-125a agomir protected the pulmonary vessels from mitochondrial dysfunction and abnormal remodeling. In the present study, we determined that mitochondrial homeostasis, particularly Mfn1, played an important role in PASMCs proliferation. MiR-125a, an important underlying factor, which inhibited Mfn1 expression and decreased PASMCs disordered growth during hypoxia. These results provide a theoretical basis for the prevention and treatment of pulmonary vascular remodeling. Key messages Hypoxia leads to upregulation of mitofusin 1 (Mfn1) both in vivo and in vitro. Mfn1 is involved in hypoxia-induced PASMCs proliferation. Mfn1-mediated mitochondrial homeostasis is regulated by miR-125a. MiR-125a plays a role in PASMCs oxidative phosphorylation and glycolysis.

Foot-and-mouth disease (FMD) remains a very serious barrier to agricultural development and the international trade of animals and animal products. Recently, serotype O has been the most prevalent FMDV serotype in China, and it has evolved into four different lineages: O/SEA/Mya-98, O/ME-SA/PanAsia, O/ME-SA/Ind-2001 and O/Cathay. PanAsia-2, belonging to the O/ME-SA topotype, is prevalent in neighbouring countries and poses the risk of cross-border spread in China. This study aimed to develop a promising vaccine candidate strain that can not only provide the best protection against all serotype O FMDVs circulating in China but also be used as an emergency vaccine for the prevention and control of transboundary incursion of PanAsia-2. Here, two chimeric FMDVs (rHN/TURVP1 and rHN/NXVP1) featuring substitution of VP1 genes of the O/TUR/5/2009 vaccine strain (PanAsia-2) and O/NXYCh/CHA/2018 epidemic strain (Mya98) were constructed and evaluated. The biological properties of the two chimeric FMDVs were similar to those of the wild-type (wt) virus despite slight differences in plaque sizes observed in BHK-21 cells. The structural protein-specific antibody titres induced by the rHN/TURVP1 and wt virus vaccines in pigs and cows were higher than those induced by the rHN/NXVP1 vaccine at 28–56 dpv. The vaccines prepared from the two chimeric viruses and wt virus all induced the production of protective cross-neutralizing antibodies against the viruses of the Mya-98, PanAsia and Ind-2001 lineages in pigs and cattle at 28 dpv; however, only the animals vaccinated with the rHN/TURVP1 vaccine produced a protective immune response to the field isolate of the Cathay lineage at 28 dpv, whereas the animals receiving the wt virus and the rHN/NXVP1 vaccines did not, although the wt virus and O/GXCX/CHA/2018 both belong to the Cathay topotype. This study will provide very useful information to help develop a potential vaccine candidate for the prevention and control of serotype O FMD in China.

Magnesium and nickel were recovered from nickel-rich serpentine through sulfation roasting and water leaching. The factors affecting the extraction percentages of Mg and Ni were discussed. Under the conditions of the ratio of acid to ore of 0.8:1 and roasting temperature of 650 °C for 120 min, 91.6% of Mg and 88.7% of Ni but only 4.8% of Fe were extracted. The roasting kinetics of Mg and Ni were investigated. The results showed that the roasting stage was governed by internal diffusion in the temperature range of 350–650 °C, and the activation energy of nickel and magnesium were different in the time ranges of 0–30 min and 60–120 min, with 17.45 kJ⋅mol−1 (0–30 min) and 14.12 kJ⋅mol−1 (60–120 min) for magnesium and 15.48 kJ⋅mol−1 (0–30 min) and 12.46 kJ⋅mol−1 (60–120 min) for nickel. The kinetic equations were obtained.

Background Abnormal lipid levels have been suggested as a mechanism leading to atherosclerosis of the lumbar vessels, resulting in low back pain (LBP). This study examined whether abnormal lipid levels were associated with LBP among middle-aged adults in Japan. Methods The present study included adults between 40 and 64 years old who underwent an annual health checkup. A total of 258,367 eligible participants were analyzed to investigate associations of LBP with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and LDL-C/HDL-C ratio. Participants were categorized into two groups according to each of LDL-C, HDL-C, and LDL-C/HDL-C ratio (LDL-C: ≥ 140 vs. < 140 mg/dL; HDL-C: ≥ 40 vs. < 40 mg/dL; LDL-C/HDL-C ratio: ≥ 2.5 vs. < 2.5). Information on LBP was obtained using a self-administered questionnaire. Logistic regression modeling was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for LBP. Results The prevalence of LBP was 2.2% in men and 2.1% in women. Multivariable analysis adjusting for age, body mass index, and lifestyle factors found significant associations for HDL-C <  40 mg/dL (OR, 1.34; 95%CI, 1.20–1.48 in men; OR, 1.32; 95%CI, 1.02–1.72 in women) and LDL-C/HDL-C ratio ≥ 2.5 (OR, 1.17; 95%CI, 1.09–1.26 in men; OR, 1.15; 95%CI, 1.03–1.29 in women) with LBP. Conclusions Low HDL-C and high LDL-C/HDL-C ratio were significantly associated with LBP in a middle-aged Japanese population. These findings might support the atherosclerosis-LBP hypothesis.