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Yue-Lin Zhang,1,2,* Tan-Yang Zhou,1,2,* Jing Ai,3,* Sheng-Qun Chen,1,2,* Feng Chen,4 Chun-Hui Nie,1,2 Xin-Hua Chen,1,2 Guan-Hui Zhou,1,2 Hong-Liang Wang,1,2 Tong-Yin Zhu,1,2 Bao-Quan Wang,1,2 Zi-Niu Yu,1,2 Li Jing,1,2 Li-Ming Wu,1,2 Shu-Sen Zheng,1,2 Jun-Hui Sun1,2 1Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People’s Republic of China; 2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, People’s Republic of China; 3Eye Centre, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Hui SunHepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, People’s Republic of ChinaTel +86 571 8723 6815Email 1307005@zju.edu.cnFeng ChenDepartment of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, People’s Republic of ChinaTel +86 571 8723 6815Email chenfenghz@zju.edu.cnPurpose: Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically modified endothelial progenitor cells (EPCs) as cellular carriers. This study applied EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer to explore its therapeutic effect.Materials and Methods: EPCs from heart blood of male BALB/c nude mice were cultured and transfected with CD and ES fusion gene. Subsequently, these genetically modified cells were injected into mice bearing hepatoma through their tail veins. The tumor volumes and cell apoptosis were followed up.Results: Tumor volume in the group injected CD/ES-EPCs greatly decreased. The positive rate of VEGF and CD31 in the tumor tissue was lowest in the CD/ES-EPC group. Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group.Conclusion: The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.Keywords: gene-targeting therapy, endothelial progenitor cell, endostatin, cytosine deaminase, hepatoma, transfection

Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear., Objective: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT., Methods: The study was conducted at a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio into the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and the incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not restricted., Results: Between September 2018 and July 2020, 163 patients were randomized to undergo DEB-TACE ( n =82) or cTACE ( n =81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 years), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0-10.0) versus 4.0 months (95% CI, 3.0-5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42-0.95; P =0.027). The DEB-TACE group showed a higher response rate [51 (66.2%) vs. 36 (46.8%); P =0.0015] and a longer median OS [12.0 months (95% CI, 9.0-16.0) vs. 8.0 months (95% CI, 7.0-11.0), P =0.039] than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combination with surgery were independently associated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AE., Conclusion: DEB-TACE is superior to cTACE in treating HCC patients with PVTT, demonstrating improved PFS and OS with an acceptable safety profile, and may thus emerge as a promising treatment strategy for HCC patients with PVTT., Trial Registration: Chinese Clinical Trial Registry ChiCTR1800018035., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia (CAP) predictors., Aim: To evaluate the association between serum activin A levels and prognosis in CAP patients., Methods: A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition, and 48 healthy individuals as the control group were enrolled in this study. Circulating concentrations of activin A were measured using enzyme-linked immunoassays. The interaction between activin A levels and etiologies of CAP was determined. Based on the severity of CAP, 110 patients (65.48%) were categorized into group-I, 42 (25%) cases were grouped into group-II, and 16 (9.52%) cases were categorized into group-III., Results: Serum activin A levels were higher in patients with CAP than controls, but independent of etiology. Moreover, the scores of Pneumonia Severity Index (PSI) and CURB-65 positively correlated with the increasing levels of serum activin A, and were at their highest peak in individuals in group-III ( P < 0.001). Combining activin A with CURB-65 or PSI was more effective in improving predictive property ( P < 0.01). According to Cox proportional regression analysis, after adjusting clinical parameters, we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients ( P < 0.001)., Conclusion: Higher level of serum activin A was associated with poor prognosis of CAP. Activin A can be used as a more valuable biomarker of prognosis in CAP patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dai, Xiao, Zhou, Ye and Han.)

Objective: To analyze the changes in optical coherence tomography angiography(OCTA)-related parameters before and after idiopathic macular hole (IMH) internal limiting membrane (ILM) flap inversion surgery and assess their impact on retinal sensitivity. Methods: A retrospective case series study was conducted, collecting clinical data of 30 patients (30 eyes) diagnosed with IMH who underwent vitrectomy combined with ILM flap inversion surgery at Shanxi Eye Hospital, affiliated with Shanxi Medical University, between January 2020 and December 2021. Visual acuity and best-corrected visual acuity were examined preoperatively and at 1, 3, and 6 months postoperatively. Microperimetry measured retinal sensitivity (RS), and OCTA measured retinal thickness (RT) as well as vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Statistical analysis was performed using t-tests, repeated measures analysis of variance, and Pearson correlation analysis. Results: Thirty patients with IMH (30 eyes) were included, with 3 males (3 eyes) and 27 females (27 eyes). The mean age was (62.5±3.0) years, and the follow-up time was (96.3±1.3) days, with a 100% closure rate of macular holes postoperatively. RT in the macular was significantly lower at 1, 3, and 6 months postoperatively compared to preoperative values ( F =46.21, P <0.001). The RT in the upper macular region showed statistically significant differences at different time points ( P <0.001). VD in the SCP layer showed no significant differences between the upper and lower macular regions at various time points ( F =3.21, P =0.601). VD in the upper region of the DCP layer increased at 1, 3, and 6 months postoperatively ( P <0.001). RS in the macular was higher at 1, 3, and 6 months postoperatively compared to preoperative values ( F =52.01, P <0.001). RS in the lower macular region increased at 3 and 6 months postoperatively ( P <0.001), while in the upper region, it increased only at 6 months postoperatively ( P <0.001). There was a positive correlation between RS and RT at 1 and 3 months postoperatively, but not at 6 months postoperatively in the upper macular region ( r =0.40, P =0.071). In the lower macular region, there was a positive correlation between RS and RT at 1 and 3 months postoperatively ( P <0.001). There was no correlation between RS in the upper macular region at 6 months postoperatively and preoperative RT ( r =0.43, P =0.072), but there was a positive correlation with RT at 3 months postoperatively ( r =0.58, P =0.041). Conclusions: After idiopathic macular hole internal limiting membrane flap inversion surgery, the OCTA-related parameters have changed. There are transient changes in deep vascular parameters and thinning of the retinal layers at the ILM inversion site, leading to decreased sensitivity.

The cultured meat technology has developed rapidly in recent years, but there are still many technical challenges that hinder the large-scale production and commercialization of cultured meat. Firstly, it is necessary to lay the foundation for cultured meat production by obtaining seed cells and maintaining stable cell functions. Next, technologies such as bioreactors are used to expand the scale of cell culture, and three-dimensional culture technologies such as scaffold culture or 3D printing are used to construct the three-dimensional structure of cultured meat. At the same time, it can reduce production costs by developing serum-free medium suitable for cultured meat. Finally, the edible quality of cultured meat is improved by evaluating food safety and sensory flavor, and combining ethical and consumer acceptability issues. Therefore, this review fully demonstrates the current development status and existing technical challenges of the cultured meat production technology with regard to the key points described above, in order to provide research ideas for the industrial production of cultured meat.

Objective: To investigate the correlation between the cross-sectional area of the macular hole (MH) cavity and the blood flow density in different retinal layers, as well as the impact of cavity size on preoperative and postoperative retinal function in patients with idiopathic macular holes (IMH). Methods: A retrospective cohort study was conducted. Clinical data were collected from 18 patients (18 eyes) diagnosed with IMH who underwent vitrectomy combined with internal limiting membrane peeling at Shanxi Eye Hospital affiliated to Shanxi Medical University from August 2019 to December 2021. Visual acuity, best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCTA), and multifocal electroretinography (mfERG) were performed preoperatively and at 1, 3, and 6 months postoperatively. Blood flow density data were collected for the overall retina, macular center fovea, and parafoveal regions, and the cavity cross-sectional area was measured using ImageJ software. Ten healthy subjects without retinal abnormalities who underwent mfERG at Shanxi Eye Hospital affiliated to Shanxi Medical University during the same period were included as a control group. One eye was randomly selected for each subject, with 5 left eyes and 5 right eyes. Statistical analysis was performed using Pearson correlation analysis, independent samples t-test, and repeated measures analysis of variance. Results: All 18 IMH patients had unilateral disease, including 3 males and 15 females, with an average age of (64.22±4.33) years and a duration of illness of 75 (38, 120) days. In the control group, consisting of 10 subjects, 4 were male and 6 were female, with an average age of (63.67±6.96) years. Preoperatively, all 18 affected eyes exhibited a macular hole cavity, which closed and disappeared one month postoperatively. The total cavity cross-sectional area was (4.84±2.28) mm2, with an average area of (0.27±0.13) mm 2 . The cavity cross-sectional area was positively correlated with the MH height ( r =0.82, P <0.001), ellipsoid zone disruption diameter ( r =0.74, P <0.001), and preoperative BCVA ( r =0.62, P =0.006). The cavity cross-sectional area was positively correlated with the blood flow density of the superficial macular center fovea ( r =0.47, P =0.049) and negatively correlated with the blood flow density of the deep retina ( r =-0.50, P =0.033) and deep parafoveal blood flow density ( r =-0.65, P =0.003). Compared to healthy eyes in the control group, IMH eyes showed decreased amplitudes of P1 and N1 waves in mfERG, prolonged P1 wave latency except at ring 1 (2.18° outward from the foveal center), and prolonged N1 wave latency except at ring 2 (7.46° outward from the foveal center) and 5 (29.75° outward from the foveal center) (all P <0.05). The cavity cross-sectional area was only related to the preoperative latency of the N1 wave at ring 2 ( r =0.64, P =0.004) and had an effect on the changes in the preoperative and postoperative latency of P1 and N1 waves at ring 1 and 5 ( F =4.94, 5.96; P =0.042, 0.027). Time changes had no effect on the preoperative and postoperative amplitudes and latencies of mfERG P1 and N1 waves (all P >0.05), but the interaction between cavity cross-sectional area and time had statistical significance for the amplitudes of P1 at ring 1 and N1 at ring 2( F =6.89, 3.76; P =0.003, 0.035). Conclusions: In patients with IMH, a larger macular hole cavity cross-sectional area is associated with lower blood flow density, particularly in the deep parafoveal region, poorer visual acuity, and decreased retinal function at 7.46° outward from the foveal center.

Background: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant., Methods: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575)., Findings: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28)., Interpretation: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults., Funding: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cultured meat is one of the meat substitutes produced through tissue engineering and other technologies. Large-scale cell culture is the key for cultured meat products to enter the market. Therefore, this study is aimed to explore the effect of long-term passage in vitro on smooth muscle cells (SMCs) and the effect of transforming growth factor-β1 (TGF-β1) on SMCs in the late passage. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage. Transcriptome results showed that the ECM pathway and aging-related signaling pathways were significantly up-regulated in the late passage period. TGF-β1 did not promote SMCs of late passage proliferation at the proliferation stage but promoted the gene and protein expression of collagen as the main protein of the extracellular matrix proteins at the differentiation stage. In addition, proteomic analysis revealed that TGF-β1 promoted the expression of cell adhesion molecules which activate the Hippo signaling pathway and the HIF-1 signaling pathway and further promoted the production of collagen-containing extracellular matrix proteins. This could provide ideas for large-scale production of cultured meat products using SMCs.

Nucleic acid detection is widely used in pathogen screening and detection due to its high sensitivity and specificity. With the increase of detection requirements and the development of amplification technology, nucleic acid detection methods are gradually developing towards simple, fast and low-cost. Quantitative polymerase chain reaction (qPCR), as the "gold standard" for nucleic acid detection, relies on expensive equipment and professional operators, which is not suitable for rapid on-site detection of pathogens. The visual detection method without relying on excitation light source or complex equipment can present the detection results in a more intuitive and portable way after combining with rapid and efficient amplification technology, which has the potential of point-of-care testing (POCT). This paper focuses on the reported application of amplification technology and CRISPR/Cas technology in visual detection and compares their advantages and disadvantages, so as to provide reference for POCT strategy based on pathogen nucleic acid.

High-fat diet (HFD)-induced obesity leads endothelial dysfunction and contributes to cardiovascular diseases. Palmitic acid (PA), a free fatty acid, is the main component of dietary saturated fat. Physcion, a chemical ingredient from Rhubarb, has been shown anti-hypertensive, anti-bacteria, and anti-tumor properties. However, the effects of physcion on endothelial dysfunction under HFD-induced obesity have not been reported. The purpose of the present study was to define the protective effect of physcion on HFD-induced endothelial dysfunction and its mechanisms involved. Obesity rat model was induced by HFD for 12 weeks. A rat thoracic aortic ring model was used to investigate the effects of physcion on HFD-induced impairment of vasorelaxation. Endothelial cell injury model was constructed in human umbilical vein endothelial cells (HUVECs) by treating with PA (0.25 mM) for 24 h. The results revealed that physcion reduced body weight and the levels of plasma TG, prevented impairment of endothelium-dependent relaxation in HFD-fed rats. In PA-injured HUVECs, physcion inhibited impaired viability, apoptosis and inflammation. Physcion also suppressed PA-induced both oxidative stress and ER stress in HUVECs. Furthermore, physcion increased PA-induced decrease in the activation of eNOS/Nrf2 signaling in HUVECs. These findings suggest that physcion has a significant beneficial effect on regulating HFD-induced endothelial dysfunction, which may be related to the inhibition of oxidative stress and ER stress through activation of eNOS/Nrf2 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cultured fat is inducing adipose progenitor cells (APCs) to differentiate into mature adipocytes for consumption. The traditional adipogenic differentiation cocktail, including insulin, dexamethasone, indomethacin, isobutylmethylxanthine and rosiglitazone, has potential food safety problems in cultured fat. Therefore, the detection of these residues is necessary to ensure food safety. In this research, a method of high performance liquid chromatography (HPLC) was established to quantitatively analyze the potential residual content of dexamethasone, indomethacin, isobutylmethylxanthine and rosiglitazone in cultured fat and medium. Quantitative analysis showed that the content of four residues in cultured fat decreased to zero on Day 10. Subsequently, enzyme-linked immunosorbent assay (ELISA) was performed to detect the insulin content in the cultured fat and found that the insulin content in the cultured fat on Day 10 was 2.78 ± 0.21 μg/kg. After soaking with phosphate buffered saline (PBS), the insulin content decreased to 1.88 ± 0.54 μg/kg. In conclusion, this research provided an effective approach to clarify the content of potential residual components in cultured fat and it will provide reference for the safety of cultured fat in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Salmonella enterica serovar Enteritidis is a common foodborne pathogen that infects both humans and animals. The S. Enteritidis virulence regulation network remains largely incomplete, and knowledge regarding the specific virulence phenotype of small RNAs (sRNAs) is limited. Here, we investigated the role of a previously identified sRNA, S almonella a dhesive- a ssociated s RNA (SaaS), in the virulence phenotype of S. Enteritidis by constructing mutant (Δ saaS ) and complemented (Δ saaS /p saaS ) strains. SaaS did not affect S. Enteritidis; it was activated in the simulated intestinal environment (SIE), regulating the expression of virulence target genes. We discovered that it directly binds ssaV mRNA. Caco-2 and RAW 264.7 cell assays revealed that SaaS promoted S. Enteritidis invasion and damage to epithelial cells while suppressing macrophage overgrowth and destruction. Furthermore, a BALB/c mouse model demonstrated that the deletion of SaaS significantly reduced mortality and attenuated the deterioration of pathophysiology, bacterial dissemination into systemic circulation, and systemic inflammation. Our findings indicate that SaaS is required for S. Enteritidis virulence and further highlight its biological role in bacterial pathogenesis. IMPORTANCE Salmonella is a zoonotic pathogen with high virulence worldwide, and sRNAs have recently been discovered to play important roles. We explored the biological characteristics of the sRNA SaaS and developed two cell infection models and a mouse infection model. SaaS is an SIE-responsive sRNA that regulates the expression of virulence-targeted genes. Additionally, it differentially mediates invasion and intracellular growth for survival and infection of the epithelium and macrophages. We further found that SaaS enhanced bacterial virulence by promoting lethality, colonization, and inflammatory response. These findings provide a better understanding of the critical role of sRNA in bacterial virulence.

Elevated levels of plasma homocysteine (Hcy) causes severe cardiac dysfunction, which is closely associated with oxidative stress. Emodin, a naturally occurring anthraquinone derivative, has been shown to exert antioxidant and anti-apoptosis activities. However, whether emodin could protect against Hcy-induced cardiac dysfunction remains unknown. The current study aimed to investigate the effects of emodin on the Hcy-induced cardiac dysfunction and its molecular mechanisms. Rats were fed a methionine diet to establish the animal model of hyperhomocysteinemia (HHcy). H9C2 cells were incubated with Hcy to induce a cell model of Hcy-injured cardiomyocytes. ELISA, HE staining, carotid artery and left ventricular cannulation, MTT, fluorescence staining, flow cytometry and western blotting were used in this study. Emodin significantly alleviated the structural damage of the myocardium and cardiac dysfunction from HHcy rats. Emodin prevented apoptosis and the collapse of MMP in the Hcy-treated H9C2 cells in vitro. Further, emodin reversed the Hcy-induced apoptosis-related biochemical changes including decreased Bcl-2/Bax protein ratio, and increased protein expression of Caspase-9/3. Moreover, emodin suppressed oxidative stress in Hcy-treated H9C2 cells. Mechanistically, emodin significantly inhibited the Hcy-activated MAPK by reducing ROS generation in H9C2 cells. Furthermore, emodin upregulated NO production by promoting the protein phosphorylation of Akt and eNOS in injured cells. The present study shows that emodin protects against Hcy-induced cardiac dysfunction by inhibiting oxidative stress via MAPK and Akt/eNOS/NO signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sleep deprivation (SD) is prevalent throughout the world, which has negative effects on cognitive abilities, and causing mood alterations. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in Lamiophlomis rotata (L. rotata) Kudo, possesses potent neuroprotective properties and analgesic effects. Here, we evaluated the alleviative effects of 8-OaS on memory impairment and anxiety in mice subjected to SD (for 72-h). Our results demonstrated that 8-OaS (0.2, 2, 20 mg/kg) administration dose-dependently ameliorated behavioral abnormalities in SD mice, accompanied with restored synaptic plasticity and reduced shrinkage and loss of hippocampal neurons. 8-OaS reduced the inflammatory response and oxidative stress injury in hippocampus caused by SD, which may be related to inhibition of NLRP3 inflammasome-mediated inflammatory process and activation of the Nrf2/HO-1 pathway. SD also led to increases in the expressions of TLR-4/MyD88, active NF-κB, pro-IL-1β, TNFα and MDA, as well as a decrease in the level of SOD in mice hippocampus, which were reversed by 8-OaS administration. Moreover, our molecular docking analyses showed that 8-OaS also has good affinity for NLRP3 and Nrf2 signaling pathways. These results suggested that 8-OaS could be used as a novel herbal medicine for the treatment of sleep loss and for use as a structural base for developing new drugs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paris spp. are important medicinal plant and main raw material for many Chinese patent medicines, but viral diseases have became serious problems in cultivation of this group of important medicinal plants in China. In this study, eight viruses were identified in the diseased plants of Paris yunnanensis by high-throughput sequencing (HTS) and RT-PCR. These viruses include three novel viruses (two potyviruses and one nepovirus), Hippeastrum chlorotic ringspot virus (HCRV), Lychnis mottle virus (LycMoV), Paris mosaic necrosis virus (PMNV), Paris virus 1 and pepper mild mottle virus. The three new viruses were tentatively named Paris potyvirus 3 (ParPV-3), Paris potyvirus 4 (ParPV-4), Paris nepovirus 1 (ParNV-1) and their complete genome sequences were determined. Sequence analyses showed ParPV-3 and ParPV-4 shared the highest amino acid (aa) sequence identities of 54.3% to each other and 53.0-57.8% to other known potyviruses. ParNV-1 had aa sequence identities of 28.8-63.7% at protease-polymerase (Pro-Pol) with other nepoviruses. Phylogenetic analyses further support that the three viruses are new members of their corresponding genera. Analyses of the partial sequences of HCRV and LycMoV infecting P. yunnanensis revealed they diverged from existing isolates by aa sequence identities of 97.1% at glycoprotein precursor of HCRV and 93.3% at polyprotein of LycMoV. These two viruses are reported for the first time in Paris spp. A total of 123 field samples collected from P. yunnanensis in four counties of Yunnan, Southwest China were tested by RT-PCR for detecting each of the eight viruses. Results showed that nearly half of the samples were positive for at least one of the eight viruses. Two potyviruses, ParPV-3 (26.8%) and PMNV (24.4%), were predominant and widely distributed in the fields, while other viruses occurred in low rates and/or had limited distribution. This study insights into the virome infecting P. yunnanensis and provides valuable information for diagnosis and control of viral diseases in P. yunnanensis., Competing Interests: G-hZ was employed by Chinese Medicine Resources Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lan, He, Yang, Zhou, Chen, Wei, Li, Gu, Li and Li.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established therapeutic option for the management of variceal hemorrhage in patients with cirrhosis. The simultaneous migration of the coil and n-butyl-2-cyanoacrylate (NBCA) is an extremely rare but significant complication after TIPS. Because of its rare presentation, there are currently no definitive recommendations for the management of this condition., Case Presentation: A 46-year-old man with hepatitis B cirrhosis underwent TIPS placement for uncontrolled gastroesophageal varix (GEV) bleeding secondary to portal hypertension in August 2018. During the procedure, large GEVs were embolized using a coil and NBCA. After a year, coil and NBCA migration into the stomach was observed. Attempts to remove the coil using biopsy forceps during esophagogastroduodenoscopy failed. The patient refused further intervention on the coil to prevent further complications and received conservative therapy instead. Close surveillance with endoscopy is recommended for detecting coils and varices., Conclusions: The present case reports an extremely rare but significant complication after TIPS, which highlights the management and follow-up recommendation for such rare complications. Our experience may provide guidance for the management of future similar cases and stimulate discussion about treatment methods of similar patients., (© 2022. The Author(s).)

Cultured meat is an emerging technology that is friendly for the environment and animal welfare. As a novel food ingredient, cultured fat is essential for the flavor and nutrition of cultured meat. In this study, we purified adipose progenitor cell (APC) from freshly isolated porcine stromal vessel fraction (SVF) by fluorescence-activated cell sorting (FACS) and identified the transcriptome characteristics of APC by RNA sequencing (RNA-seq). The results showed that APC had characteristics of high-efficiency proliferation and adipogenic differentiation and was distinct from SVF cell in transcriptome profiles. Subsequently, APC was used to prepare cultured fat by 3D bioprinting and to evaluate the differences in fatty acid composition between cultured fat and porcine subcutaneous adipose tissue (pSAT). The results indicated that the fatty acid composition and content of cultured fat had a certain similarity with pSAT; specifically, the content of key monounsaturated fatty acid (MUFA) that create pork flavor in cultured fat, such as C18:1(n-12), C18:1(n-9) and C19:1(n-9)T, were close to that of pSAT. Therefore, this research indicated that APC is a promising candidate cell type for the production of cultured fat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cultured meat technology is a promising new technology to solve the negative problems brought by traditional animal husbandry. Cultured meat should be further developed to appear on consumers' tables as alternative protein product. Therefore, this study used food grade peanut wire-drawing protein as scaffold to culture smooth muscle cells (SMCs) in vitro to obtain cultured meat productions containing both animal protein and plant protein. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage, which means that the plasticity of cells decreased in the later stage of passage. SMCs can well adhere to the peanut wire-drawing protein scaffold and produce extracellular matrix protein and muscle protein, so as to form a cultured meat product with rich protein composition. This study provides a theoretical basis for the production of nutrient-rich cultured meat products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Stemness decline of muscle stem cells (MuSCs) is a significant problem in cultured meat processing. In the present study, three flavonoids (quercetin, icariin, and 3,2'-dihydroxyflavone) with multi concentrations were evaluated to promote the proliferation and differentiation of porcine muscle stem cells. In the proliferation phase, 3,2'-dihydroxyflavone (10 μM) significantly amplified the cells by 34% and up-regulated the expression of paired box transcription factor 7 (PAX7) by 60%, which was higher than quercetin (75 nM) and icariin (7.5 nM). In the differentiation phase, quercetin (50 nM) showed the best pro-differentiation effect and up-regulated the expression of myosin heavy chain (MYHC) by 4.73-fold compared with the control group. These results indicated that flavonoids had a significant impact on promoting the proliferation and differentiation of porcine MuSCs, and 3,2'-dihydroxyflavone (10 μM) for proliferation and quercetin (50 nM) for differentiation were the optimal combinations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cultured meat is an emergent technology that cultivates cells in three-dimensional scaffolds to generate tissue for consumption. Fat makes an important contribution to the flavor and texture of traditional meat, but there are few reports on cultured fat. Here, we demonstrated the construction of cultured fat by inoculating porcine adipose-derived mesenchymal stem cell (ADSC) on peanut wire-drawing protein (PWP) scaffolds. First, we demonstrated that basic fibroblast growth factor (bFGF) promoted cell proliferation and maintained adipogenic differentiation ability. Then, we generated cultured fat and found that cultured fat decreased the texture of PWP scaffolds. Moreover, 43 volatile compounds were detected by headspace gas chromatography-ion mobility spectrometry (GC-IMS), of which 17 volatile compounds showed no significant differences between cultured fat and porcine subcutaneous adipose tissue (pSAT), which indicated that cultured fat and pSAT had certain similarities. Collectively, this research has great promise for improving the quality of cultured meat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

To investigate the effects of ultrasonic treatment on proteolysis and taste development of defective dry-cured ham, sensory attributes, enzyme activities, protein degradation and free amino acids were evaluated after different ultrasonic treatments. The ultrasonic treatment of 1000 W & 50 °C significantly increased the intensities of overall taste, umami, sweetness and richness, and decreased bitterness values compared with other groups. The residual activities of DPP I and cathepsin B + L in 1000 W & 50 °C maintained 48.71% and 24.94% of control group, respectively; the intense degradation of structural proteins was observed by label-free proteomics, accordingly. The contents of total free amino acids from 4522.64 mg/100 g muscles in control group increased to 5838.75 mg/100 g muscles in 1000 W & 50 °C; the largest increase of sweet and umami amino acids observed in 1000 W & 50 °C was responsible for the improvement of taste quality of defective dry-cured ham., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cultivating meat is a promising solution to the negative problems brought by traditional animal husbandry. To make cultured meat have the sensory and nutritional characteristics of conventional meat as much as possible, many studies have been conducted on various cell types and scaffold characteristics. Therefore, this study aims to produce a low-cost cultured meat with a quality closer to that of conventional meat. Tissue generation requires three-dimensional (3D) scaffolds to support cells and simulate extracellular matrix (ECM). Here, we used peanut wire-drawing protein (a biomaterial based on edible porous protein) as a new culture meat scaffold to culture cells. The scaffold can support cell attachment and proliferation to create 3D engineered porcine muscle tissue. The differentiation of smooth muscle cells (SMCs) was induced by a low serum medium to produce more extracellular matrix proteins. After differentiation, it was found that peanut wire-drawing protein scaffolds could be used for porcine smooth muscle cell adhesion and growth. The ECM protein and muscle protein produced by SMCs can endow cultured meat with better quality. This technology provides an innovative pathway for the industrialized production of cultured meat., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

γ-Lycorane, a degradation product of the Aromaticaceae alkaloid lycorine, is one of the most attractive molecules in the Aromaticaceae family. It remains a popular target for synthesis due to its pentacyclic structure, which presents a vehicle for demonstrating the utility of new synthetic strategies. Various synthetic methods have been developed by synthetic chemists since the first synthesis of γ-lycorane by Nasuo in 1966. Thus, this review presents an overview of the literature on the ways utilized within the synthesis of γ-lycorane in racemic and enantiopure forms via electrophilic arylation, Pd-catalyzed C-C coupling, Bischler-Napieralski cyclization, Pictet-Spengler cyclization, photocyclization, radical cyclization, chiral pool synthesis, chiral auxiliary-mediated synthesis, and catalytic asymmetric synthesis, ranging from 1966 to 2022., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Breast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments., Patients and Methods: A total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram., Results: Nomograms were constructed for the breast NEC and breast IDC groups after PSM. The C-index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818-0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone., Conclusions: We established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC., (Copyright © 2022. Published by Elsevier Inc.)

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

Cardiac hypertrophy is a common myocardial structural abnormality which may cause heart failure. Many studies have shown that cardiac hypertrophy can be induced by hyperthyroidism. Ligand-gated potassium channels have been reported to be involved in various biological processes in the cardiovascular system, such as GPCR coupled K ACh and metabolism sensor K ATP channel. It is unclear whether the gene expression of K ACh and K ATP was altered in hyperthyroid rabbit atria. We aimed to investigate the expression of K ACh and K ATP genes in rabbit atria in our experimental model. We established an effective hyperthyroidism-induced cardiac hypertrophy animal model through an injection of T4. H&E staining and RT-PCR were used to observe the histomorphological damages and alteration of gene expression. The results showed that the heart weight, heart rate significantly increased in T4-treated rabbits. The systolic pressure increased from 115.60 mmHg to 152.6 mmHg in T4-treated rabbits. The expression of K ACh and K ATP genes was decreased in the atria of hyperthyroidism-induced cardiac hypertrophied rabbits. These findings indicated that the decreased gene expression of K ACh and K ATP may be related to hyperthyroidism-induced cardiac hypertrophy and atrial fibrillation., Competing Interests: None., (IJCEP Copyright © 2022.)

While the research on improving the meat quality of cultured meat is in full swing, few studies have focused on the effect of smooth muscle cells (SMCs) on the meat quality of cultured meat. Therefore, this study aimed at building a cultured meat model containing smooth muscle cells, and further evaluating the effect of smooth muscle cells on the quality of cultured meat, so as to reveal the contribution of smooth muscle cells in the production of cultured meat. In this study, we isolated high purity of smooth muscle cells from vascular tissues. The addition of basic fibroblast growth factor (bFGF) to the medium significantly increased the growth rate of smooth muscle cells and the expression of extracellular matrix related genes, especially collagen and elastin. Smooth muscle cells were seeded in a collagen gel to construct a culture meat model. It was found that the pressure loss of the model meat significantly decreased from 98.5 % in control group to 54 % with the extension of culture time for 9 days, while the total collagen content of model meat increased significantly (P < 0.05). In addition, the hydrogel tissue with smooth muscle cells compacted more dramatically and were more tightly, accompanied by significantly increased hardness, springiness and chewiness compared to the control one (P < 0.05). These results indicate that smooth muscle cells can secrete extracellular matrix proteins such as collagen, which can significantly enhance the texture of cultured meat models prepared by hydrogel., (Copyright © 2021. Published by Elsevier Ltd.)

Aim: The purpose of our study was to conduct a retrospective analysis to compare the effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with cirrhosis with or without portal vein thrombosis (PVT). Methods: We included a total of 203 cirrhosis patients successfully treated with TIPS between January 2015 and January 2018, including 72 cirrhosis patients with PVT (35.5%) and 131 without PVT (64.5%). Our subjects were followed for at least 1 year after treatment with TIPS. Data were collected to estimate the mortality, shunt dysfunction, and complication rates after TIPS creation. Results: During the mean follow-up time of 19.5 ± 12.8 months, 21 (10.3%) patients died, 15 (7.4%) developed shunt dysfunction, and 44 (21.6%) experienced overt hepatic encephalopathy (OHE). No significant differences in mortality ( P = 0.134), shunt dysfunction ( P = 0.214), or OHE ( P = 0.632) were noted between the groups. Age, model for end-stage liver disease (MELD) score, and refractory ascites requiring TIPS were risk factors for mortality. A history of diabetes, percutaneous transhepatic variceal embolization (PTVE), 8-mm diameter stent, and platelet (PLT) increased the risk of shunt dysfunction. The prevalence of variceal bleeding and recurrent ascites was comparable between the two groups (16.7 vs. 16.7% P = 0.998 and 2.7 vs. 3.8% P = 0.678, respectively). Conclusions: Transjugular intrahepatic portosystemic shunts are feasible in the management of cirrhosis with PVT. No significant differences in survival or shunt dysfunction were noted between the PVT and no-PVT groups. The risk of recurrent variceal bleeding, recurrent ascites, and OHE in the PVT group was generally similar to that in the no-PVT group. TIPS represents a potentially feasible treatment option in cirrhosis patients with PVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Lu, Zhang, Nie, Zhou, Zhou, Zhu, Wang, Chen, Yu, Jing and Sun.)

BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selection between the approaches remains controversial. OBJECTIVE. The purpose of this study was to compare DEB-TACE and cTACE in the treatment of patients with unresectable HCC in terms of hepatobiliary changes on imaging and clinical complications. METHODS. This retrospective study included 1002 patients (871 men, 131 women; mean age, 59 ± 12 years) from three centers who had previously untreated unresectable HCC and underwent DEB-TACE with epirubicin (780 procedures in 394 patients) or cTACE with ethiodized oil mixed with doxorubicin and oxaliplatin (1187 procedures in 608 patients) between May 2016 and November 2018. Among these patients 83.4% had hepatitis B-related liver disease, 57.6% had Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC, and 42.4% had three or more nodules. Mean tumor size was 6.3 ± 4.2 cm. Hepatobiliary changes and tumor response were evaluated with CT or MRI 1 month after TACE. Clinical records were reviewed for adverse events. RESULTS. Bile duct dilatation ( p < .001) and portal vein narrowing ( p = .006) on imaging and liver failure ( p = .03) and grade 3 abdominal pain ( p < .001) in clinical follow-up occurred at higher frequency in the DEB-TACE group (15.5%, 4.6%, 2.3%, and 6.1%) than in the cTACE (7.4%, 1.6%, 0.7%, and 2.1%) group. Higher frequency of bile duct dilation in patients who underwent DEB-TACE was observed in subgroup analyses that included patients with BCLC stage A or B HCC ( p = .001), with cirrhosis ( p < .001), without cirrhosis ( p = .04), and without main portal vein tumor thrombus ( p = .002). Total bilirubin level 1 month after treatment was 1.5 ± 2.4 mg/dL (95% CI, 1.2-1.8 mg/dL) for DEB-TACE versus 1.3 ± 2.0 mg/dL (95% CI, 1.1-1.5 mg/dL) for cTACE ( p = .02). The cTACE and DEB-TACE groups did not differ in other manifestations of postembolization syndrome or systemic toxicity ( p > .05). Local tumor disease control rates did not differ between the cTACE and DEB-TACE groups (1 month, 96.7% vs 98.5%, p = .06; 3 months, 81.8% vs 82.4%, p = .87), but overall DCR was significantly higher in the cTACE than in the DEB-TACE group (1 month, 87.5% vs 80.0%, p = .001; 3 months, 78.5% vs 72.1%, p = .02). CONCLUSION. Compared with cTACE, DEB-TACE was associated with greater frequency of hepatobiliary injury and severe abdominal pain. CLINICAL IMPACT. Greater caution and closer follow-up are warranted for patients who undergo DEB-TACE for unresectable HCC than for those who undergo cTACE.

Purpose: The aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery., Methods: A total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Nomograms and risk stratification models were constructed., Results: Patients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668-0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627-0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568-0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509-0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709-1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713-1.275], P = 0.737)., Conclusion: Older female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigated the effect of frozen storage periods (0, 2, 4, 6, or 8 weeks) of raw meat and stewing on the flavor of chicken broth. With the increased storage duration of frozen raw material, the contents of the free amino acids, nucleotides and mineral elements in the broth decreased significantly, especially within the first 4 weeks, and then increased significantly. Meanwhile, the volatile compounds showed the reverse trend. The results from the E-nose, E-tongue and sensory evaluation indicated a progressive difference in overall flavor profiles between the samples. The sensory scores of the meaty and fatty traits reached a maximum as raw chicken meat was stored for 4 weeks at -18 °C, which should be related to the increased contents of aldehydes and 2-pentyl furan. Overall, the limited storage duration of frozen raw meat can enhance the flavor of chicken broth., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Excessive bitterness, pastiness, and adhesiveness are the main organoleptic and textural defects of dry-cured ham, which often cause a lot of financial losses to manufacturers and seriously damage the quality of the product. These sensory and textural defects are related to the protein degradation of dry-cured ham. Proteomics shows great potential to improve our understanding of the molecular mechanism of sensory and textural defects and identify biomarkers for monitoring their quality traits. This review presents some of the major achievements and considerations in organoleptic and textural defects of dry-cured ham by proteomics analysis in the recent decades and gives an overview about how to correct sensory and textural defects of dry-cured ham. Proteomics reveals that muscle proteins derived from myofibril and cytoskeleton and involved in metabolic enzymes and oxygen transport have been identified as potential biomarkers in defective dry-cured ham. Relatively high residual activities of cathepsin B and L are responsible for the excessive degradation of these protein biomarkers in defective dry-cured ham. Ultrasound-assisted mild thermal or high-pressure treatment shows a good correction for the organoleptic and textural defects of dry-cured ham by changing microstructure and conformation of muscle proteins by accelerating degradation of proteins and polypeptides into free amino acids., (© 2021 Institute of Food Technologists®.)

Objective : To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors. Method : Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS. Results : The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage. Conclusion : DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This study evaluated the texture of hog maw and the degradation of Types I and III collagen in the intramuscular connective tissue (IMCT) of hog maw at different cooking temperatures (75-95°C) and times (50-130 min). The cooking loss, shear force, collagen content, collagen solubility, and IMCT strength of hog maw cooked in water baths were measured. The instrumental texture profile analysis showed that the brittleness, springiness, chewiness and hardness of the cooked hog maw significantly increased with the increase of cooking temperature, while the hardness, springiness and chewiness increased first and then decreased with increasing cooking time. Cooking loss exhibited a 38% increase between the raw meat and meat cooked at 95°C. The collagen solubility significantly increased from 5.5 mg/g for raw meat to 8.6 mg/g for meat cooked at 95°C, accompanied by decreases in the shear force and IMCT strength associated with the increase in cooking temperature and time. These results show that the texture and collagen characteristics of hog maw are dramatically affected by the cooking temperature and time. Sodium dodecyl sulfate electrophoresis and immunofluorescence staining further showed that collagen degradation occurred after cooking, and the degradation of Type I collagen was higher than that of Type III collagen. These results indicated that the degradation of Type I collagen was mainly responsible for the sensory and textural improvements of the cooked hog maw., (© 2020 Wiley Periodicals LLC.)

Background: Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties., Purpose: The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved., Study Design and Methods: Hyperhomocysteinemia (HHcy) rat model was induced by feeding 3% methionine. A rat thoracic aortic ring model was used to investigate the effects of physcion on Hcy-induced impairment of endothelium-dependent relaxation. Two doses, low (L, 30 mg/kg/day) and high (H, 50 mg/kg/day) of physcion were used in the present study. To construct Hcy-injured human umbilical vein endothelial cells (HUVECs) model, the cells treated with 3 mM Hcy. The effects of physcion on Hcy-induced HUVECs cytotoxicity and apoptosis were studied using MTT and flow cytometry. Confocal analysis was used to determine the levels of intracellular Ca 2+ . The levels of protein expression of the apoptosis-related markers Bcl-2, Bax, caspase-9/3, and Akt and endothelial nitric oxide synthase (eNOS) were evaluated by western blot., Results: In the HHcy rat model, plasma levels of Hcy and malondialdehyde (MDA) were elevated (20.45 ± 2.42 vs. 4.67 ± 1.94 μM, 9.42 ± 0.48 vs. 3.47 ± 0.59 nM, p < 0.001 for both), whereas superoxide dismutase (SOD) and nitric oxide (NO) levels were decreased (77.11 ± 4.78 vs. 115.02 ± 5.63 U/ml, 44.51 ± 4.45 vs. 64.18 ± 5.34 μM, p < 0.001 and p < 0.01, respectively). However, treatment with physcion significantly reversed these changes (11.82 ± 2.02 vs. 20.45 ± 2.42 μM, 5.97 ± 0.72 vs. 9.42 ± 0.48 nM, 108.75 ± 5.65 vs. 77.11 ± 4.78 U/ml, 58.14 ± 6.02 vs. 44.51 ± 4.45 μM, p < 0.01 for all). Physcion also prevented Hcy-induced impairment of endothelium-dependent relaxation in HHcy rats (1.56 ± 0.06 vs. 15.44 ± 2.53 nM EC 50 for ACh vasorelaxation, p < 0.05 vs. HHcy). In Hcy-injured HUVECs, physcion inhibited the impaired viability, apoptosis and reactive oxygen species. Hcy treatment significantly increased the protein phosphorylation levels of p38 (2.26 ± 0.20 vs. 1.00 ± 0.12, p <0.01), ERK (2.11 ± 0.21 vs. 1.00 ± 0.11, p <0.01) and JNK. Moreover, physcion reversed the Hcy-induced apoptosis related parameter changes such as decreased mitochondrial membrane potential (MMP) and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9/3 in HUVECs. Furthermore, the downregulation of Ca 2+ , Akt, eNOS and NO caused by Hcy were recovered with physcion treatment in HUVECs., Conclusion: Physcion prevents Hcy-induced endothelial dysfunction by activating Ca 2+ - and Akt-eNOS-NO signaling pathways. This study provides the first evidence that physcion might be a candidate agent for the prevention of cardiovascular disease induced by Hcy., (Copyright © 2020. Published by Elsevier GmbH.)

Objectives: To explore the outcomes of combined transarterial chemoembolization (TACE) with sorafenib in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) and to establish a prognostic prediction nomogram to differentiate target patients and stratify risk., Materials and Methods: This multicentre, retrospective study consisted of 185 consecutive treatment-naïve patients with HCC and PVTT treated with TACE plus sorafenib from three institutions between January 1st, 2012 and December 31st, 2017. The primary outcome measurement of the study was overall survival (OS). The type of PVTT was classified by the Liver Cancer Study Group of Japan. The prognostic nomogram was established based on the predictors and was performed with interval validation., Results: The median OS of the Vp1-3 and Vp4 groups was 12.4 months (11.7-18.9) and 8.5 months (7.6-11.2) (P = 0.00098), respectively, and there was a significant difference in the median OS between the Vp1-2 and Vp3 subgroups (16.4 months (12.2-27.9) vs. 10.9 months (8.4-18.1), P = 0.041). The multivariate Cox regression analysis suggested that tumour size, albumin-bilirubin grade, and PVTT type were independent prognostic factors. The C-index value of the nomogram based on these predictors in the entire cohort was 0.731 (0.628-0.833)., Conclusions: After the combined therapy of TACE and sorafenib, advanced HCC patients with segmental or subsegmental PVTT showed better survival than those with main PVTT. The nomogram can be applied to identify advanced HCC patients with PVTT who may benefit most from the combination treatment and be helpful for making decision in clinical practice.

High-pressure processing (HPP) can modify the construction of interfacial proteins (IPs) to improve the properties of reduced-fat and reduced-salt (RFRS) meat batters. In this study, the relationship between the construction of IPs and their solubility at fat droplet/water interface in RFRS meat batters with HPP treatments was investigated. When 200 MPa for 2 min was applied, the IPs exhibited the highest solubility due to a high concentration of absorbed myosin with the content of random coil 65.62%, but the particle diameter was in reverse. The microscopy revealed the depolymerization of IPs occurred at low pressure, while macromolecular aggregates were produced as the cross-linking of IPs to some degree at pressure ≥ 200 MPa. This phenomenon was supported by the result of SDS-PAGE and the sulfhydryl of IPs. In conclusion, the HPP induced solubility alteration of IPs was achieved by modifying their construction through adjusting the secondary structures and regulating bond interactions., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: To establish albumin-bilirubin (ALBI) grade-based and Child-Turcotte-Pugh (CTP) grade-based nomograms, as well as to develop an artificial neural network (ANN) model to compare the prognostic performance and discrimination of these two grades for hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as an initial treatment., Methods: This multicenter retrospective study included patients from three hospitals between January 2013 and August 2018. In the training cohort, independent risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The nomograms and ANN were established and then validated in two validation cohorts., Results: A total of 504 patients (319, 61, and 124 patients from hospitals A, B, and C, respectively) were included. The median OS was 15.2, 26.9, and 14.8 months in the training cohort and validation cohorts 1 and 2, respectively (P = 0.218). In the training cohort, both ALBI grade and CTP grade were identified as independent risk factors. The ALBI grade-based and CTP grade-based nomograms were established separately and showed similar prognostic performance and discrimination when validated in the validation cohorts (C-index in validation cohort 1: 0.799 vs. 0.779, P = 0.762; in validation cohort 2: 0.700 vs. 0.693, P = 0.803). The ANN model showed that the ALBI grade had higher importance in survival prediction than the CTP grade., Conclusions: The ALBI grade and CTP grade have comparable prognostic performance for HCC patients treated with TACE combined with sorafenib. ALBI grades 1 and 2 have the potential to act as a stratification factor for clinical trials on the combination therapy of TACE and systemic therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JJ declared a past co-authorship with several of the authors B-YZ, J-HS, G-HZ and C-FN to the handling editor., (Copyright © 2020 Zhong, Yan, Sun, Zhang, Hou, Yang, Zhou, Wang, Li, Huang, Zhang, Zhu and Ni.)

Cone-rod dystrophy (CORD) is an inherited retinal degenerative disease characterized by progressive loss of cone and rod photoreceptors. Although several genes have been reported to cause autosomal dominant CORD (adCORD), the genetic causes of adCORD have not been fully elucidated. Here, we identified the ATP1A3 gene, encoding the α3 subunit of Na + , K + -ATPase, as a novel gene associated with adCORD. Using whole-exome sequencing (WES), we found a candidate mutation of ATP1A3 that co-segregated with the disease in an analysis of two affected patients and one healthy relative in an adCORD family. According to our RNA-seq data, we demonstrated that the Atp1a3 mRNA level was extremely high in the murine retina. Overexpression of mutant ATP1A3 in vitro led to a reduced oxygen consumption rate (OCR), reflecting the limited mitochondrial reserve capacity. Furthermore, we generated transgenic mice expressing the ATP1A3 cDNA with patient variant and found decreased electroretinogram (ERG) responses. Moreover, the mutant ATP1A3 is highly expressed in photoreceptor inner segment, where mitochondria are enriched. These results suggest that the ATP1A3 mutation is a new genetic cause responsible for adCORD and indicate that ATP1A3 plays an important role in retinal function.

Objectives: To develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib., Methods: This retrospective multicenter study consisted of 201 patients with treatment-naïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction., Results: The median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023)., Conclusion: The deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib., (Copyright © 2020 Zhang, Xia, Yan, Sun, Zhong, Hou, Yang, Zhou, Wang, Zhao, Jian, Huang, Zhang, Zhang, Zhang, Li, Zhu, Gao and Ni.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an ongoing pandemic of new coronavirus pneumonia (corona virus disease 2019, COVID-19). The virus has a long incubation period and strong infectivity, which poses a major threat to global health and safety. Detection of SARS-CoV-2 nucleic acid lies at the center of rapid detection of COVID-19, which is instrumental for mitigation of the ongoing pandemic. As of August 17, 2020, The National Medical Products Administration in China has approved 15 new coronavirus nucleic acid detection kits, 10 kits of which are based on reverse transcription-real-time quantitative PCR (RT-qPCR) technology. The remaining kits use five molecular diagnostic technologies different from RT-qPCR. This article reviews the principles, reaction time, advantages and disadvantages of above 15 detection kits, in order to provide references for rapid screening, diagnosis, prevention and control of COVID-19 and similar infectious diseases.

Objective: To investigate the efficacy of shunt after transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis accompanied with portal vein thrombosis (PVT). Methods: Forty-four cases with liver cirrhosis accompanied with PVT who underwent TIPS treatment from January 2015 to May 2018 were retrospectively analyzed. Clinical baseline data of the patients were collected. Portal vein pressure gradient (PVPG) before and after the surgery was recorded. Shunt patency was observed at 3, 6, 12, 18 and 24 months after the surgery. The influencing factors were determined by univariate and multivariate analysis. Results: Transjugular intrahepatic portosystemic shunt was successfully established in all 44 cases. The postoperative PVPG was lower than preoperative ( P < 0.01). The shunt patency rate after TIPS in PVT was 18.2% ( n = 8). The cumulative shunt patency rates at 3, 6, 12, 18, and 24 months after surgery were 95.5%, 90.7%, 90.7%, 86.8% and 74.4%, respectively. Univariate analysis showed that diabetes history, platelet level and prothrombin time-international normalized ratio were associated with postoperative shunt dysfunction. Multivariate analysis showed that diabetes history ( P = 0.007, OR = 28.606) was an independent risk factor for postoperative shunt dysfunction. Conclusion: TIPS is a safe and feasible procedure, which can effectively reduce the portal pressure in liver cirrhosis accompanied with PVT. Diabetic patients have a higher risk of postoperative shunt dysfunction. Therefore, clinical intervention should be strengthened for high-risk patients.

Introduction: The care for patients with hepatocellular carcinoma (HCC) is challenging. This study is to evaluate the effect of adjuvant transarterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage A HCC patients after hepatectomy., Methods: Consecutive HCC patients with BCLC stage A, treated by hepatectomy alone (HA) or hepatectomy with TACE (HT), were retrospectively enrolled. Propensity score matching (PSM) was used to balance baseline differences. The recurrence-free survival (RFS) and overall survival (OS) were evaluated using the Kaplan-Meier. The impact of TACE on survival outcome was determined by Cox hazard regression., Results: After PSM, 230 patients (115 HT and 115 HA) were enrolled in the analysis. The 1-, 3-, and 5-year RFS rates were 87.0, 63.5, and 50.4%, respectively, for the HT group, and 87.8, 67.0, and 58.3% for the HA group. The OS rates at 1-, 3-, and 5-year were 99.1, 93.9, and 87%, respectively, for the HT group, and 100, 92.2, and 88.7% for the HA group. No significant differences were seen in either the RFS (log-rank test, χ 2 = 0.891, p = 0.345) or OS (log-rank test, χ 2 = 0.146, p = 0.702) between the specific pairs of two groups. Cox regression identified that TACE was not the factor affecting RFS or OS ( p = 0.399; HR 0.847; 95% CI 0.576-1.245 for RFS vs. p = 0.989; HR 0.995; 95% CI 0.471-2.100 for OS)., Conclusion: Our data indicate that TACE is not an effective intervention in the adjuvant setting for BCLC stage A HCC after hepatectomy., (Copyright © 2020 Zhang, Nie, Chen, Zhou, Zhou, Zhu, Chen, Chen, Wang, Wang, Yu, Jing, He and Sun.)

Objective: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys., Materials and Methods: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure., Results: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure., Conclusion: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed., Competing Interests: None

Background: The metastasis of laryngeal nerve lymph node is mostly found in the upper-and middle esophageal cancer, the ratio of esophageal length from the upper incisors to the position where the esophageal tumor began to appear as proven via endoscopy to the height (LH) is likely to affect the possibility of detection of recurrent laryngeal nerve(RLN) lymph node (LN) metastasis. The purpose of this study was to evaluate the predictive value of LH for RLN LN metastasis., Methods: One hundred and eighty-eight patients (mean age: 64.89 years; range: 46-84 years) calculated LH before esophagectomy and LN dissection were retrospective analyzed. The clinicopathological data of the patients, LH calculations were compared with the RLN LN histopathologic results to investigate the effect of LH on the diagnosis of RLN LN metastasis., Results: The LH correlated with that of the RLN LN metastasis in receiver-operating-characteristic (ROC) analysis. Our ROC analyses demonstrated the optimal cut-off value was 16.66 for LH with an area under the curve value of 0.69. Compared with the Height (H) and L, ROC curve for LH have better performance in predicting the RLN LN metastasis., Conclusions: LH is a useful predictive tool in the evaluation of RLN LN metastasis for esophageal cancer. The present findings support the result that LH can be an indicator of RLN LN dissection.

To better understand the contribution of myosin light chain (MLC) isoforms to sensory defects in Jinhua ham, dipeptidyl peptidase (DPP) activities, peptide fragments, cleavage sites and the potential of DPP to develop sensory defects of dry-cured ham were evaluated and discussed in normal and defective hams. Higher residual activities of DPP I were found in defective ham compared with normal ham; approximate 3-fold peptide fragments were identified in defective ham than in normal ham. These regions of positions 11-35 and 116-141 in MLC 1, 13-53 and 139-156 in MLC 2, and 18-50 in MLC 3 contributed to the intense generation of peptide fragments in defective ham. PLS-DA further revealed DPP I showing intense response to degrade peptides. Cleavage sites including Glu-128, Tyr-132 and Glu-133 were responsible for the intense release of dipeptides in defective ham. These cleavages could play key role in discriminating taste attributes between defective and normal hams., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)