SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Bone union and mobility outcomes for reconstructed open tibial fractures: a plastic surgical experience from a major trauma center.

Introduction: The goal in open tibial fracture management is to achieve a united tibia in an extremity that allows pain free mobilization. The objective of this study was to assess factors that lead to this functional outcome in lower limb reconstruction, from a plastic surgical perspective. Materials and methods: The Plastic and Reconstructive Surgery lower limb database at a tertiary trauma hospital was searched for open tibial injuries from February 2015 to March 2020. The nature and severity of injury, timing and details of all operations including reconstructions were collected prospectively. Mobility including gait aids, pain, and complications were retrospectively collected. Union was assessed in two ways, depending on fracture location. Metaphyseal and diaphyseal tibial fractures were provided mRUST scores (union defined as RUST > 13) and epiphyseal tibial fractures were categorically classified as "united" or "non-union" by two independent radiologists. Results: During the five-year study period there were 148 open leg injuries in the database. Twenty-one patients underwent a primary amputation due to severity of their initial injury. One hundred patients underwent primary limb salvage. Sixty-one patients in the limb salvage group achieved primary tibial union with a mean follow-up time of 19.4 months post injury. Twenty-three additional patients were confirmed to subsequently unite. Patient who achieved union were more likely to mobilise without gait aids. Discussion: In this study definitive external fixation and soft tissue infection were both associated with higher rates of non-union. Longer times to soft tissue reconstruction was not associated with an increase in acute soft tissue complications. More importantly bone union, pain and mobility did not decline. After undertaking a primary limb salvage pathway for 100 patients, the ultimate tibial fracture union rate was 84% and the confirmed ambulation rate was 96%.

Traditional Chinese medicine formulae: A complementary method for the treatment of polycystic ovary syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine condition that significantly affects women of all age groups and is characterized by metabolic dysfunction. The efficacy of existing pharmaceutical interventions for the treatment of PCOS remains inadequate. With a rich history and cultural significance spanning thousands of years, Traditional Chinese Medicine (TCM) is extensively employed for treating a variety of ailments and can serve as a supplementary therapy for managing PCOS. Multiple clinical observations and laboratory tests have unequivocally demonstrated the substantial effectiveness and safety of TCM formulae in treating PCOS, and further investigations are currently in progress. AIM OF THE STUDY: To summarize the TCM formulae commonly employed in the clinical management of PCOS, examine their therapeutic benefits, investigate their mechanism of action, active constituents, and establish the correlation between efficacy, mechanism of action, and active constituents. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Web of Science, and China national knowledge infrastructure (CNKI) using the following keywords: "Polycystic Ovary Syndrome", "Traditional Chinese Medicine Decoctions", "Traditional Chinese Medicine formulae", "Traditional Chinese Medicine", "Clinical Observation", "Mechanism", "Treatment", "Pharmacology", and various combinations of these terms. From January 1, 2006 until October 7, 2023, (inclusive). RESULTS: This paper summarized the clinical effectiveness, mechanism of action, and active components of 8 TCM formulae for the treatment of PCOS. Our research indicates that TCM formulae can potentially treat PCOS by enhancing the levels of hyperandrogenism and other endocrine hormones, decreasing insulin resistance and hyperinsulinemia, and controlling chronic low-grade inflammation, among other modes of action. In addition, we found an association between epigenetics and TCM formulae for the treatment of PCOS. CONCLUSION: TCM formulae have specific advantages in the treatment of Polycystic Ovary Syndrome (PCOS). They achieve therapeutic benefits by targeting several pathways and connections, attracting considerable interest and playing a vital role in the treatment of PCOS. TCM formulae can be used as an adjunctive therapy for the treatment of PCOS.

Optical coherence tomography angiography manifestations of different degrees of nonproliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P&#x0026;#x003C;0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P&#x0026;#x003C;0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

A Dual GLP-1/GIP Receptor Agonist Is More Effective than Liraglutide in the A53T Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a complex syndrome with many elements, such as chronic inflammation, oxidative stress, mitochondrial dysfunction, loss of dopaminergic neurons, build-up of alpha-synuclein (α-syn) in cells, and energy depletion in neurons, that drive the disease. We and others have shown that treatment with mimetics of the growth factor glucagon-like peptide 1 (GLP-1) can normalize energy utilization, neuronal survival, and dopamine levels and reduce inflammation. Liraglutide is a GLP-1 analogue that recently showed protective effects in phase 2 clinical trials in PD patients and in Alzheimer disease patients. We have developed a novel dual GLP-1/GIP receptor agonist that can cross the blood-brain barrier and showed good protective effects in animal models of PD. Here, we test liraglutide against the dual GLP-1/GIP agonist DA5-CH (KP405) in the A53T tg mouse model of PD which expresses a human-mutated gene of α-synuclein. Drug treatment reduced impairments in three different motor tests, reduced levels of α-syn in the substantia nigra, reduced the inflammation response and proinflammatory cytokine levels in the substantia nigra and striatum, and normalized biomarker levels of autophagy and mitochondrial activities in A53T mice. DA5-CH was superior in almost all parameters measured and therefore may be a better drug treatment for PD than liraglutide.

Biogeographic diversification of Actaea (Ranunculaceae): Insights into the historical assembly of deciduous broad-leaved forests in the Northern Hemisphere.

The deciduous broad-leaved forests (DBLFs) cover large temperate and subtropical high-altitude regions in the Northern Hemisphere. They are home to rich biodiversity, especially to numerous endemic and relict species. However, we know little about how this vegetation in the Northern Hemisphere has developed through time. Here, we used Actaea (Ranunculaceae), an herbaceous genus almost exclusively growing in the understory of the Northern Hemisphere DBLFs, to shed light on the historical assembly of this biome in the Northern Hemisphere. We present a complete species-level phylogenetic analysis of Actaea based on five plastid and nuclear loci. Using the phylogenetic framework, we estimated divergence times, ancestral ranges, and diversification rates. Phylogenetic analyses strongly support Actaea as monophyletic. Sections Podocarpae and Oligocarpae compose a clade, sister to all other Actaea. The sister relationship between sections Chloranthae and Souliea is strongly supported. Section Dichanthera is not monophyletic unless section Cimicifuga is included. Actaea originated in East Asia, likely the Qinghai-Tibet Plateau, in the late Paleocene (c. 57 Ma), and subsequently dispersed into North America in the middle Eocene (c. 43 Ma) via the Thulean bridge. Actaea reached Europe twice, Japan twice, and Taiwan once, and all these five colonization events occurred in the late Miocene-early Pliocene, a period when sea level dropped. Actaea began to diversify at c. 43 Ma. The section-level diversification took place at c. 27-37 Ma and the species-level diversification experienced accelerations twice, which occurred at c. 15 Ma and c. 5 Ma, respectively. Our findings suggest that the Northern Hemisphere DBLFs might have risen in the middle Eocene and further diversified in the late Eocene-Oligocene, middle Miocene and early Pliocene, in association with climatic deterioration during these four periods.

EPOR activation attenuates colitis via enhancing LC3B-dependent apoptotic cell clearance.

Systemic immune activation and excessive inflammatory response, induced by intestinal barrier damage, are the major characteristics of inflammatory bowel disease (IBD). Excessive apoptotic cell accumulation leads to the production of a large number of inflammatory factors, further aggravating IBD development. Gene set enrichment analysis data showed that the homodimeric erythropoietin receptor (EPOR) was highly expressed in the whole blood of patients with IBD. EPOR is specifically expressed in intestinal macrophages. However, the role of EPOR in IBD development is unclear. In this study, we found that EPOR activation significantly alleviated colitis in mice. Furthermore, in vitro, EPOR activation in bone marrow-derived macrophage (BMDMs) promoted microtubule-associated protein 1 light chain 3B (LC3B) activation and mediated the clearance of apoptotic cells. Moreover, our data showed that EPOR activation facilitated the expression of phagocytosis- and tissue-repair-related factors. Our findings suggest that EPOR activation in macrophages promotes apoptotic cell clearance, probably via LC3B-associated phagocytosis (LAP), providing a new mechanism for understanding pathological progression and a novel potential therapeutic target for colitis.

A Case Study of Chimeric Antigen Receptor T Cell Function: Donor Therapeutic Differences in Activity and Modulation with Verteporfin.

BACKGROUND: Chimeric antigen receptor (CAR) T cells have recently been demonstrated to extract and express cognate tumor antigens through trogocytosis. This process may contribute to tumor antigen escape, T cell exhaustion, and fratricide, which plays a central role in CAR dysfunction. We sought to evaluate the importance of this effect in epidermal growth factor receptor variant III (EGFRvIII) specific CAR T cells targeting glioma. METHODS: EGFRvIII-specific CAR T cells were generated from various donors and analyzed for cytotoxicity, trogocytosis, and in vivo therapeutic activity against intracranial glioma. Tumor autophagy resulting from CAR T cell activity was evaluated in combination with an autophagy inducer (verteporfin) or inhibitor (bafilomycin A1). RESULTS: CAR T cell products derived from different donors induced markedly divergent levels of trogocytosis of tumor antigen as well as PD-L1 upon engaging target tumor cells correlating with variability in efficacy in mice. Pharmacological facilitation of CAR induced-autophagy with verteporfin inhibits trogocytic expression of tumor antigen on CARs and increases CAR persistence and efficacy in mice. CONCLUSION: These data propose CAR-induced autophagy as a mechanism counteracting CAR-induced trogocytosis and provide a new strategy to innovate high-performance CARs through pharmacological facilitation of T cell-induced tumor death.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Anatomic study and clinical application of iliac crest chimeric tissue flap / 中国修复重建外科杂志

OBJECTIVE@#To conduct anatomical study on the iliac crest chimeric tissue flap and summarize its effectiveness of clinical application in repairing limb wounds.@*METHODS@#Latex perfusion and anatomical study were performed on 6 fresh adult cadaver specimens with 12 sides, to observe the initial location, distribution, quantity, and direction of the common circumflexa iliac artery, the deep circumflexa iliac artery, and the superficial circumflexa iliac artery, and to measure their initial external diameter. Between December 2020 and September 2022, the iliac crest chimeric tissue flap repair was performed on 5 patients with soft tissue of limbs and bone defects. There were 3 males and 2 females, with an average age of 46 years (range, 23-60 years). Among them, there were 3 cases of radii and skin soft tissue defects and 2 cases of tibia and skin soft tissue defects. The length of bone defects was 4-8 cm and the area of skin soft tissue defects ranged from 9 cm×5 cm to 15 cm×6 cm. The length of the iliac flap was 4-8 cm and the area of skin flap ranged from 12.0 cm×5.5 cm to 16.0 cm×8.0 cm. The donor sites were directly sutured.@*RESULTS@#Anatomical studies showed that there were 10 common circumflex iliac arteries in 5 specimens, which originated from the lateral or posterolateral side of the transition between the external iliac artery and the femoral artery, with a length of 1.2-1.6 cm and an initial external diameter of 0.8-1.4 mm. In 1 specimen without common circumflexa iliac artery, the superficial and deep circumflex iliac arteries originated from the external iliac artery and the femoral artery, respectively, while the rest originated from the common circumflex iliac artery. The length of superficial circumflex iliac artery was 4.6-6.7 cm, and the initial external diameter was 0.4-0.8 mm. There were 3-6 perforator vessels along the way. The length of deep circumflex iliac artery was 7.8-9.2 cm, and the initial external diameter was 0.5-0.7 mm. There were 3-5 muscular branches, 4-6 periosteal branches, and 2-3 musculocutaneous branches along the way. Based on the anatomical observation results, all iliac crest chimeric tissue flaps were successfully resected and survived after operation. The wounds at recipient and donor sites healed by first intention. All patients were followed up 8-24 months, with an average of 12 months. The tissue flap has good appearance and soft texture. X-ray film reexamination showed that all the osteotomy healed, and no obvious bone resorption was observed during follow-up.@*CONCLUSION@#The common circumflex iliac artery, deep circumflex iliac artery, and superficial circumflex iliac artery were anatomically constant, and it was safe and reliable to use iliac crest chimeric tissue flap in repairing the soft tissue and bone defects of limbs.

Analysis of dust monitoring results of dust exposure enterprises in Shenxian from 2017 to 2020 / 中华劳动卫生职业病杂志

Objective: In order to understand the dust concentration in the workplace of dust exposure enterprises in Shenxian. To evaluate the degree of occupational hazard factors of dust exposure enterprises. And provide basis for the formulation of occupational protection standards and management system of dust exposure enterprises. Methods: In February 2022, the dust concentration monitoring data of 89 dust exposure enterprises from 2017 to 2020 by the Shenxian Center for Disease Control and Prevention were collected, and the qualified rates of dust concentration detection of dust exposure enterprises in different years, dust types and enterprise sizes were analyzed. Results: A total of 89 dust enterprises were monitored from 2017 to 2020, 2132 dust samples were collected, and 1818 qualified samples were taken, with a total qualified rate of 85.3%. From 2017 to 2020, the dust detection qualified rates showed a year-by-year increase trend, 78.7% (447/568), 84.1% (471/560), 88.6% (418/472) and 90.6% (482/532), respectively, with statistically significant differences (χ(2)=36.27, P=0.003). The differences in the qualified rates of dust detection samples of silicon dust (66.1%, 41/62), grain dust (86.7%, 1549/1786), cotton dust (84.1%, 106/126) and wood dust (77.2%, 122/158) were statistically significant (χ(2)=29.66, P=0.002). The qualified rate of dust samples in large and medium-sized enterprises (95.1%, 1194/1256) was higher than that of small-sized enterprises (71.2%, 624/876), and the difference was statistically significant (χ(2)=1584.40, P=0.001) . Conclusion: The qualified rate of dust concentration monitoring results of dust exposure enterprises in Shenxian showed an increase trend year by year, while the pualified rate of dust concentration monitoring in small-sized enterprises was low, and the occupational hazard of silica dust was still severe.

In-hospital outcomes of SARS-CoV-2-infected health care workers in the COVID-19 pandemic first wave, Quebec, Canada.

BACKGROUND: Health care workers (HCW), particularly immigrants and ethnic minorities are at increased risk for SARS-CoV-2 infection. Outcomes during a COVID-19 associated hospitalization are not well described among HCW. We aimed to describe the characteristics of HCW admitted with COVID-19 including immigrant status and ethnicity and the associated risk factors for Intensive Care unit (ICU) admission and death. METHODS: Adults with laboratory-confirmed community-acquired COVID-19 hospitalized from March 1 to June 30, 2020, at four tertiary-care hospitals in Montréal, Canada were included. Demographics, comorbidities, occupation, immigration status, country of birth, ethnicity, workplace exposures, and hospital outcomes (ICU admission and death) were obtained through a chart review and phone survey. A Fine and Gray competing risk proportional hazards model was used to estimate the risk of ICU admission among HCW stratified by immigrant status and region of birth. RESULTS: Among 1104 included persons, 150 (14%) were HCW, with a phone survey participation rate of 68%. HCWs were younger (50 vs 64 years; p<0.001), more likely to be female (61% vs 41%; p<0.001), migrants (68% vs 55%; p<0.01), non-White (65% vs 41%; p<0.001) and healthier (mean Charlson Comorbidity Index of 0.3 vs 1.2; p<0.001) compared to non-HCW. They were as likely to be admitted to the ICU (28% vs 31%; p = 0.40) but were less likely to die (4% vs. 17%; p<0.001). Immigrant HCW accounted for 68% of all HCW cases and, compared to Canadian HCW, were more likely to be personal support workers (PSW) (54% vs. 33%, p<0.01), to be Black (58% vs 4%) and to work in a Residential Care Facility (RCF) (59% vs 33%; p = 0.05). Most HCW believed that they were exposed at work, 55% did not always have access to personal protective equipment (PPE) and 40% did not receive COVID-19-specific Infection Control (IPAC) training. CONCLUSION: Immigrant HCW were particularly exposed to COVID-19 infection in the first wave of the pandemic in Quebec. Despite being young and healthy, one third of all HCW required ICU admission, highlighting the importance of preventing workplace transmission through strong infection prevention and control measures, including high COVID-19 vaccination coverage.

Functioning tailor-made 3D-printed vascular graft for hemodialysis.

BACKGROUND: The two ends of arteriovenous graft (AVG) are anastomosed to the upper limb vessels by surgery for hemodialysis therapy. However, the size of upper limb vessels varies to a large extent among different individuals. METHODS: According to the shape and size of neck vessels quantified from the preoperative computed tomography angiographic scan, the ethylene-vinyl acetate (EVA)-based AVG was produced in H-shape by the three-dimensional (3D) printer and then sterilized. This study investigated the function of this novel 3D-printed AVG in vitro and in vivo. RESULTS: This 3D-printed AVG can be implanted in the rabbit's common carotid artery and common jugular vein with ease and functions in vivo. The surgical procedure was quick, and no suture was required. The blood loss was minimal, and no hematoma was noted at least 1 week after the surgery. The blood flow velocity within the implanted AVG was 14.9 ± 3.7 cm/s. Additionally, the in vitro characterization experiments demonstrated that this EVA-based biomaterial is biocompatible and possesses a superior recovery property than ePTFE after hemodialysis needle cannulation. CONCLUSIONS: Through the 3D printing technology, the EVA-based AVG can be tailor-made to fit the specific vessel size. This kind of 3D-printed AVG is functioning in vivo, and our results realize personalized vascular implants. Further large-animal studies are warranted to examine the long-term patency.

Development and validation of an RNA sequencing panel for gene fusions in soft tissue sarcoma.

Gene fusions are one of the most common genomic alterations in soft tissue sarcomas (STS), which contain more than 70 subtypes. In this study, a custom-designed RNA sequencing panel including 67 genes was developed and validated to identify gene fusions in STS. In total, 92 STS samples were analyzed using the RNA panel and 95.7% (88/92) successfully passed all the quality control parameters. Fusion transcripts were detected in 60.2% (53/88) of samples, including three novel fusions (MEG3-PLAG1, SH3BP1-NTRK1, and RPSAP52-HMGA2). The panel demonstrated excellent analytic accuracy, with 93.9% sensitivity and 100% specificity. The intra-assay, inter-assay, and personnel consistencies were all 100.0% in four samples and three replicates. In addition, different variants of ESWR1-FLI, COL1A1-PDGFB, NAB2-STAT6, and SS18-SSX were also identified in the corresponding subtypes of STS. In combination with histological and molecular diagnosis, 14.8% (13/88) patients finally changed preliminary histology-based classification. Collectively, this RNA panel developed in our study shows excellent performance on RNA from formalin-fixed, paraffin-embedded samples and can complement DNA-based assay, thereby facilitating precise diagnosis and novel fusion detection.

Oral administration of Lactobacillus delbrueckii enhances intestinal immunity through inducing dendritic cell activation in suckling piglets.

Lactobacillus delbrueckii (LAB) has been demonstrated to exert versatile beneficial effects on modulating intestinal immunity, increasing gut microbial diversity, promoting growth performance, and even preventing disease onset in pigs. However, the underlying mechanism of LAB-mediated gut immunity regulation in piglets remains unclear. In this study, we found that supplementation of LAB significantly increases serum TNF-α, ileum IL-4, and IL-10 levels compared with the control group. Meanwhile, oral supplementation of LAB-modified gut microbial communities was evidenced by the increased abundance of the Lactobacillus genus in the colon. Mechanistically, LAB induced dendritic cell (DC) maturation and activation, which may be relevant to the activation of NF-κB and MAPK signaling pathways. Moreover, we found that oral administration of LAB during the suckling period shows long-lasting immunomodulatory impacts on intestinal immunity after weaning. Collectively, this study uncovers the mechanism of LAB in regulating the intestinal immunity of piglets, suggesting that LAB can be developed as an immunoenhancing biological agent during the suckling period.

CsiLAC4 modulates boron flow in Arabidopsis and Citrus via high-boron-dependent lignification of cell walls.

The mechanisms underlying plant tolerance to boron (B) excess are far from fully understood. Here we characterized the role of the miR397-CsiLAC4/CsiLAC17 (from Citrus sinensis) module in regulation of B flow. Live-cell imaging techniques were used in localization studies. A tobacco transient expression system tested modulations of CsiLAC4 and CsiLAC17 by miR397. Transgenic Arabidopsis were generated to analyze the biological functions of CsiLAC4 and CsiLAC17. CsiLAC4's role in xylem lignification was determined by mRNA hybridization and cytochemistry. In situ B distribution was analyzed by laser ablation inductively coupled plasma mass spectrometry. CsiLAC4 and CsiLAC17 are predominantly localized in the apoplast of tobacco epidermal cells. Overexpression of CsiLAC4 in Arabidopsis improves the plants' tolerance to boric acid excess by triggering high-B-dependent lignification of the vascular system's cell wall and reducing free B content in roots and shoots. In Citrus, CsiLAC4 is expressed explicitly in the xylem parenchyma and is modulated by B-responsive miR397. Upregulation of CsiLAC4 in Citrus results in lignification of the xylem cell walls, restricting B flow from xylem vessels to the phloem. CsiLAC4 contributes to plant tolerance to boric acid excess via high-B-dependent lignification of cell walls, which set up a 'physical barrier' preventing B flow.

Blind Watermarking for Hiding Color Images in Color Images with Super-Resolution Enhancement.

This paper presents a novel approach for directly hiding the pixel values of a small color watermark in a carrier color image. Watermark embedding is achieved by modulating the gap of paired coefficient magnitudes in the discrete cosine transform domain according to the intended pixel value, and watermark extraction is the process of regaining and regulating the gap distance back to the intensity value. In a comparison study of robustness against commonly encountered attacks, the proposed scheme outperformed seven watermarking schemes in terms of zero-normalized cross-correlation (ZNCC). To render a better visual rendition of the recovered color watermark, a generative adversarial network (GAN) was introduced to perform image denoising and super-resolution reconstruction. Except for JPEG compression attacks, the proposed scheme generally resulted in ZNCCs higher than 0.65. The employed GAN contributed to a noticeable improvement in perceptual quality, which is also manifested as high-level ZNCCs of no less than 0.78.

Study on mechanism of curcumol against liver fibrosis based on autophagy and apoptosis of hepatic stellate cells / 中国中药杂志

The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-β1(TGF-β1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-β1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-β1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-β1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-β1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-β1 group. As demonstrated by TEM, compared with the TGF-β1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-β1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.