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Fulltext Genetic Identification of Edible Bird's Nest in Thailand Based on ARMS-PCR

Lv D, Fan Y, Zhong W, Lonan P, Liu K, Wu M, et al.

Front Genet, 2021;12:632232.
PMID: 33763113 DOI: 10.3389/fgene.2021.632232

Edible bird's nest (EBN) is a popular delicacy in the Asian Pacific region originating from Indonesia, Malaysia, Thailand and Vietnam, which consist of various potential medicine value in Traditional Chinese Medicine (TCM). Thailand is one of the main exporters of EBN. However, the genetic information of EBN, a key part of molecular biology, has yet to be reported in Thailand. It is necessary to explore the genetic information of EBN in Thailand based on a quick and simple method to help protect the rights and interests of consumers. This research aimed to systematically evaluate different methods of extracting EBN DNA to improve the efficiency of the analysis of cytochrome b (Cytb) and NADH dehydrogenase subunit 2 (ND2) gene sequences, the establishment of phylogenetic trees, and the genetic information of EBN in Thailand. Additionally, we aimed to develop a quick and simple method for identifying EBN from different species based on the genetic information and amplification-refractory mutation system PCR (ARMS-PCR). By comparing the four methods [cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), kit and guanidinium isothiocyanate methods] for EBN extraction, we found that the guanidinium isothiocyanate method was the optimal extraction method. Phylogenetic trees generated on the basis of Cytb and ND2 gene analyses showed that 26 samples of house EBN and 4 samples of cave EBN came from Aerodramus fuciphagus and Aerodramus maximus, respectively. In addition, to distinguish different samples from different species of Apodiformes, we designed 4 polymerase chain reaction (PCR) amplification primers based on the ND2 gene sequences of A. fuciphagus and A. maximus. The ARMS-PCR results showed band lengths for A. fuciphagus EBN of 533, 402, and 201 bp, while those for A. maximus EBN were 463, 317, and 201 bp. Collectively, the results showed that ARMS-PCR is a fast and simple method for the genetic identification of EBN based on designing specific original identification primers.
Molecular mechanisms underlying lignocellulose degradation and antibiotic resistance genes removal revealed via metagenomics analysis during different agricultural wastes composting

Ma C, Lo PK, Xu J, Li M, Jiang Z, Li G, et al.

Bioresour Technol, 2020 Oct;314:123731.
PMID: 32615447 DOI: 10.1016/j.biortech.2020.123731

In this study, the differences on the physico-chemical parameters, lignocellulose degradation, dynamic succession of microbial community, gene expression of carbohydrate-active enzymes and antibiotics resistance genes were compared during composting systems of bagasse pith/pig manure (BP) and manioc waste/pig manure (MW). The results revealed that biodegradation rates of organic matter, cellulose, hemicellulose and lignin (29.14%, 17.53%,45.36% and 36.48%) in BP were higher than those (15.59%, 16.74%, 41.23% and 29.77%) in MW. In addition, the relative abundance of Bacillus, Luteimonas, Clostridium, Pseudomonas, Streptomyces and expression of genes encoding carbohydrate- active enzymes in BP were higher than those in MW based on metagenomics sequencing. During composting, antibiotics and antibiotic resistance genes were substantially reduced, but the removal efficiency was divergent in the both samples. Taken together, metagenomics analysis was a potential method for evaluating lignocellulose's biodegradation process and determining the elimination of antibiotic and antibiotic resistance genes from different composting sources of biomass.
Fulltext Preparation and Characterization of Polyphenylsulfone (PPSU) Membranes for Biogas Upgrading

Kujawski W, Li G, Van der Bruggen B, Pedišius N, Tonkonogij J, Tonkonogovas A, et al.

Materials (Basel), 2020 Jun 25;13(12).
PMID: 32630434 DOI: 10.3390/ma13122847

Asymmetric polyphenylsulfone (PPSU) membranes were fabricated by a non-solvent induced phase inversion method. Glycerin and silica nanoparticles were added into the polymer solution to investigate their effects on the material properties and gas separation performance of prepared membranes. The morphology and structure of PPSU membranes were analyzed by scanning electron microscopy (SEM), the surface roughness of the selective layer was analyzed by atomic force microscopy (AFM), and the surface free energy was calculated based on the contact angle measurements by using various solvents. The gas separation performance of PPSU membranes was estimated by measuring the permeability of CO2 and CH4. The addition of glycerin as a nonsolvent into the polymer solution changed the cross-section structure from finger-like structure into sponge-like structure due to the delayed liquid-liquid demixing process, which was confirmed by SEM analysis. The incorporation of silica nanoparticles into PPSU membranes slightly increased the hydrophilicity, which was confirmed by water contact angle results. PPSU membrane fabricated from the polymer solution containing 10 wt.% glycerin showed the best CO2/CH4 selectivity of 3.86 and the CO2 permeability of 1044.01 Barrer. Mixed matrix PPSU membrane containing 0.1 wt.% silica nanoparticles showed the CO2/CH4 selectivity of 3.16 and the CO2 permeability of 1202.77 Barrer.
Estrogen directly stimulates LHb expression at the pituitary level during puberty in female zebrafish

Li G, Tang H, Chen Y, Yin Y, Ogawa S, Liu M, et al.

Mol Cell Endocrinol, 2018 02 05;461:1-11.
PMID: 28801227 DOI: 10.1016/j.mce.2017.08.003

The LHb expression is up-regulated during puberty in female zebrafish. However, the molecular mechanism underlying how LHb expression is regulated during puberty remains largely unknown. In this study, we found that the mRNA expression levels of lhb, fshb and cyp19a1b were up-regulated along with the puberty onset in zebrafish. Among the three nuclear estrogen receptors (nERs), the esr2b is the only type whose expression is significantly up-regulated during puberty onset in the pituitary. However, in situ hybridization results revealed that lhb mRNA was colocalized with esr1 and esr2a but not esr2b. Exposure to estradiol (E2) significantly stimulates LHb expression in both wild-type and kiss1-/-;kiss2-/-;gnrh3-/- triple knockout pubertal zebrafish. Moreover, exposure of cultured pituitary cells to E2 increased the LHb expression, indicating that the estrogenic effect on LHb expression could be acted at the pituitary level. Finally, we cloned and analyzed the promoter of lhb by luciferase assay. Our results indicated that the E2 responsive regions of lhb promoter for ERα and ERβ2 are identical, suggesting that ERα and ERβ2 could bind to the same half ERE region of the promoter of lhb, exhibiting a classical ERE-dependent pathway. In summary, we demonstrate that E2 could directly act on the pituitary level to stimulate LHb transcription during puberty in zebrafish.
Fulltext A soft artificial muscle driven robot with reinforcement learning

Yang T, Xiao Y, Zhang Z, Liang Y, Li G, Zhang M, et al.

Sci Rep, 2018 09 28;8(1):14518.
PMID: 30266999 DOI: 10.1038/s41598-018-32757-9

Soft robots driven by stimuli-responsive materials have their own unique advantages over traditional rigid robots such as large actuation, light weight, good flexibility and biocompatibility. However, the large actuation of soft robots inherently co-exists with difficulty in control with high precision. This article presents a soft artificial muscle driven robot mimicking cuttlefish with a fully integrated on-board system including power supply and wireless communication system. Without any motors, the movements of the cuttlefish robot are solely actuated by dielectric elastomer which exhibits muscle-like properties including large deformation and high energy density. Reinforcement learning is used to optimize the control strategy of the cuttlefish robot instead of manual adjustment. From scratch, the swimming speed of the robot is enhanced by 91% with reinforcement learning, reaching to 21 mm/s (0.38 body length per second). The design principle behind the structure and the control of the robot can be potentially useful in guiding device designs for demanding applications such as flexible devices and soft robots.
Effects of simple knee sleeves on pain and knee adduction moment in early unilateral knee osteoarthritis

Mohd Sharif NA, Usman J, Wan Safwani WKZ, Siew Li G, Abdul Karim S, Mohamed NA, et al.

Proc Inst Mech Eng H, 2019 Nov;233(11):1132-1140.
PMID: 31597554 DOI: 10.1177/0954411919874614

Knee sleeves are often prescribed to alleviate pain in people with early knee osteoarthritis. However, the biomechanics underlying their pain-relieving effect are still not well understood. This pre-post study aims at evaluating and comparing the effects of two different types of knee sleeves on knee adduction moment. Patients with clinically diagnosed knee osteoarthritis were recruited from the University of Malaya Medical Centre and were randomly assigned to two test groups using (1) a simple knee sleeve and (2) a simple sleeve with patella cutout. Knee adduction moment was collected using the Vicon motion capture system with two Kistler force plates. Pain, stiffness and physical functions were recorded using the Western Ontario and McMaster Universities Osteoarthritis Index. All measurements were taken before, immediately after and at the completion of 6 weeks of application (primary time point). In total, 17 participants with early unilateral knee osteoarthritis (47.7 (9.7) years) completed the study. Overall results show significant reduction in pain, early stance and late stance knee adduction moment and increased walking speed after 6 weeks of both knee sleeves application. This study results suggest that knee sleeves can reduce knee adduction moments in early unilateral knee osteoarthritis by 14.0% and 12.1% using the simple sleeve and the sleeve with patella cutout, respectively, and can potentially delay disease progression. In addition, knee sleeve with patella cutout does not provide additional benefits when compared to the simple knee sleeve.
Phytoremediation of cadmium from soil, air and water

Li G, Yan L, Chen X, Lam SS, Rinklebe J, Yu Q, et al.

Chemosphere, 2023 Apr;320:138058.
PMID: 36746249 DOI: 10.1016/j.chemosphere.2023.138058

Potentially toxic elements (PTEs) pose a great threat to ecosystems and long-term exposure causes adverse effects to wildlife and humans. Cadmium induces a variety of diseases including cancer, kidney dysfunction, bone lesions, anemia and hypertension. Here we review the ability of plants to accumulate cadmium from soil, air and water under different environmental conditions, focusing on absorption mechanisms and factors affecting these. Cadmium possess various transport mechanisms and pathways roughly divided into symplast and apoplast pathway. Excessive cadmium concentrations in the environment affects soil properties, pH and microorganism composition and function and thereby plant uptake. At the same time, plants resist cadmium toxicity by antioxidant reaction. The differences in cadmium absorption capacity of plants need more exploration to determine whether it is beneficial for crop breeding or genetic modification. Identify whether plants have the potential to become hyperaccumulator and avoid excessive cadmium uptake by edible plants. The use of activators such as wood vinegar, GLDA (Glutamic acid diacetic acid), or the placement of earthworms and fungi can speed up phytoremediation of plants, thereby reducing uptake of crop varieties and reducing human exposure, thus accelerating food safety and the health of the planet.
Degradation of MicroRNA miR-466d-3p by Japanese Encephalitis Virus NS3 Facilitates Viral Replication and Interleukin-1β Expression

Jiang H, Bai L, Ji L, Bai Z, Su J, Qin T, et al.

J Virol, 2020 07 16;94(15).
PMID: 32461319 DOI: 10.1128/JVI.00294-20

Japanese encephalitis virus (JEV) infection alters microRNA (miRNA) expression in the central nervous system (CNS). However, the mechanism contributing to miRNA regulation in the CNS is not known. We discovered global degradation of mature miRNA in mouse brains and neuroblastoma (NA) cells after JEV infection. Integrative analysis of miRNAs and mRNAs suggested that several significantly downregulated miRNAs and their targeted mRNAs were clustered into an inflammation pathway. Transfection with miRNA 466d-3p (miR-466d-3p) decreased interleukin-1β (IL-1β) expression and inhibited JEV replication in NA cells. However, miR-466d-3p expression increased after JEV infection in the presence of cycloheximide, indicating that viral protein expression reduced miR-466d-3p expression. We generated all the JEV coding proteins and demonstrated NS3 helicase protein to be a potent miRNA suppressor. The NS3 proteins of Zika virus, West Nile virus, and dengue virus serotype 1 (DENV-1) and DENV-2 also decreased miR-466d-3p expression. Results from helicase-blocking assays and in vitro unwinding assays demonstrated that NS3 could unwind pre-miR-466d and induce miRNA dysfunction. Computational models and an RNA immunoprecipitation assay revealed arginine-rich domains of NS3 to be crucial for pre-miRNA binding and degradation of host miRNAs. Importantly, site-directed mutagenesis of conserved residues in NS3 revealed that R226G and R202W reduced the binding affinity and degradation of pre-miR-466d. These results expand the function of flavivirus helicases beyond unwinding duplex RNA to degrade pre-miRNAs. Hence, we revealed a new mechanism for NS3 in regulating miRNA pathways and promoting neuroinflammation.IMPORTANCE Host miRNAs have been reported to regulate JEV-induced inflammation in the CNS. We found that JEV infection could reduce expression of host miRNA. The helicase region of the NS3 protein bound specifically to miRNA precursors and could lead to incorrect unwinding of miRNA precursors, thereby reducing the expression of mature miRNAs. This observation led to two major findings. First, our results suggested that JEV NS3 protein induced miR-466d-3p degradation, which promoted IL-1β expression and JEV replication. Second, arginine molecules on NS3 were the main miRNA-binding sites, because we demonstrated that miRNA degradation was abolished if arginines at R226 and R202 were mutated. Our study provides new insights into the molecular mechanism of JEV and reveals several amino acid sites that could be mutated for a JEV vaccine.
Fulltext Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD)

Hu T, Zheng Y, Zhang Y, Li G, Qiu W, Yu J, et al.

BMC Microbiol, 2012;12:305.
PMID: 23268691 DOI: 10.1186/1471-2180-12-305

The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA--random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method.
Fulltext Molecular epidemiology demonstrates that imported and local strains circulated during the 2014 dengue outbreak in Guangzhou, China

Li G, Pan P, He Q, Kong X, Wu K, Zhang W, et al.

Virol Sin, 2017 Feb;32(1):63-72.
PMID: 28120220 DOI: 10.1007/s12250-016-3872-8

The dengue virus (DENV) is a vital global public health issue. The 2014 dengue epidemic in Guangzhou, China, caused approximately 40,000 cases of infection and five deaths. We carried out a comprehensive investigation aimed at identifying the transmission sources in this dengue epidemic. To analyze the phylogenetics of the 2014 dengue strains, the envelope (E) gene sequences from 17 viral strains isolated from 168 dengue patient serum samples were sequenced and a phylogenetic tree was reconstructed. All 17 strains were serotype I strains, including 8 genotype I and 9 genotype V strains. Additionally, 6 genotype I strains that were probably introduced to China from Thailand before 2009 were widely transmitted in the 2013 and 2014 epidemics, and they continued to circulate until 2015, with one affinis strain being found in Singapore. The other 2 genotype I strains were introduced from the Malaya Peninsula in 2014. The transmission source of the 9 genotype V strains was from Malaysia in 2014. DENVs of different serotypes and genotypes co-circulated in the 2014 dengue outbreak in Guangzhou. Moreover, not only had DENV been imported to Guangzhou, but it had also been gradually exported, as the viruses exhibited an enzootic transmission cycle in Guangzhou.
High-Performance Diamond Phototransistor with Gate Controllable Gain and Speed

Ge L, Li B, Li G, Wang X, Cheong KY, Peng Y, et al.

J Phys Chem Lett, 2023 Jan 19;14(2):592-597.
PMID: 36633457 DOI: 10.1021/acs.jpclett.2c03637

This paper presents a fabricated solar-blind phototransistor based on hydrogen-terminated diamond. The phototransistor shows a large photocurrent and enhancement of responsivity over conventional two-terminal diamond-based photodetector. These enhancement effects are owing to the internal gain of the phototransistor. The fabricated phototransistor exhibits a high photoresponsivity (R) of 2.16 × 104 A/W and a detectivity (D*) of 9.63 × 1011 jones, with gate voltage (VG) and drain voltage of approximately -1.5 V and -5 V, respectively, under 213 nm light illumination. Even at ultralow operating voltage of -0.01 V, the device records satisfactory performance with R and D* of 146.7 A/W and 6.19 × 1010 jones, respectively. By adjusting the VG, photocurrent generation in the device can be continuously tuned from the fast photoconductive effect to the optical gating effect with high optical gain. When VG increases from 1.4 to 2.4 V, the decay time decreases from 1512.0 to 25.5 ms. Therefore, responsivity, dark current, Iphoto/Idark, and decay time of the device can be well tuned by VG.
Fulltext Hard-Carbon Negative Electrodes from Biomasses for Sodium-Ion Batteries

Lu B, Lin C, Xiong H, Zhang C, Fang L, Sun J, et al.

Molecules, 2023 May 11;28(10).
PMID: 37241775 DOI: 10.3390/molecules28104027

With the development of high-performance electrode materials, sodium-ion batteries have been extensively studied and could potentially be applied in various fields to replace the lithium-ion cells, owing to the low cost and natural abundance. As the key anode materials of sodium-ion batteries, hard carbons still face problems, such as poor cycling performance and low initial Coulombic efficiency. Owning to the low synthesis cost and the natural presence of heteroatoms of biomasses, biomasses have positive implications for synthesizing the hard carbons for sodium-ion batteries. This minireview mainly explains the research progress of biomasses used as the precursors to prepare the hard-carbon materials. The storage mechanism of hard carbons, comparisons of the structural properties of hard carbons prepared from different biomasses, and the influence of the preparation conditions on the electrochemical properties of hard carbons are introduced. In addition, the effect of doping atoms is also summarized to provide an in-depth understanding and guidance for the design of high-performance hard carbons for sodium-ion batteries.
The discovery of 1, 3-diamino-7H-pyrrol[3, 2-f]quinazoline compounds as potent antimicrobial antifolates

Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.

Eur J Med Chem, 2022 Jan 15;228:113979.
PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979

The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.
Fulltext Bioinspired soft robots for deep-sea exploration

Li G, Wong TW, Shih B, Guo C, Wang L, Liu J, et al.

Nat Commun, 2023 Nov 04;14(1):7097.
PMID: 37925504 DOI: 10.1038/s41467-023-42882-3

The deep ocean, Earth's untouched expanse, presents immense challenges for exploration due to its extreme pressure, temperature, and darkness. Unlike traditional marine robots that require specialized metallic vessels for protection, deep-sea species thrive without such cumbersome pressure-resistant designs. Their pressure-adaptive forms, unique propulsion methods, and advanced senses have inspired innovation in designing lightweight, compact soft machines. This perspective addresses challenges, recent strides, and design strategies for bioinspired deep-sea soft robots. Drawing from abyssal life, it explores the actuation, sensing, power, and pressure resilience of multifunctional deep-sea soft robots, offering game-changing solutions for profound exploration and operation in harsh conditions.
Fulltext Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial

Zhang X, Yip TC, Wong GL, Leow WX, Liang LY, Lim LL, et al.

Gut, 2023 Nov 24;72(12):2364-2371.
PMID: 37549979 DOI: 10.1136/gutjnl-2023-330269

OBJECTIVE: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes.
DESIGN: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year.
RESULTS: Between May 2020 and Oct 2021, 1379 patients were screened, of whom 533 and 528 were assigned to the intervention and control groups, respectively. A total of 55 out of 165 (33.3%) patients with increased fibrosis scores in the intervention group received appropriate care, compared with 4 of 131 (3.1%) patients in the control group (difference 30.2% (95% CI 22.4% to 38%); p<0.001). Overall, 11 out of 533 (2.1%) patients in the intervention group and 1 out of 528 (0.2%) patients in the control group were confirmed to have advanced liver disease (difference 1.9% (95% CI 0.61% to 3.5%); p=0.006).
CONCLUSION: Automated fibrosis score calculation and electronic reminders can increase referral of patients with type 2 diabetes and abnormal fibrosis scores at non-hepatology settings.
TRIAL REGISTRATION NUMBER: NCT04241575.
MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease

Cheung JTK, Zhang X, Wong GL, Yip TC, Lin H, Li G, et al.

Aliment Pharmacol Ther, 2023 Dec;58(11-12):1194-1204.
PMID: 37724633 DOI: 10.1111/apt.17722

BACKGROUND: Early screening may prevent fibrosis progression in metabolic-associated fatty liver disease (MAFLD).
AIMS: We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients.
METHODS: This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula.
RESULTS: MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p
Fulltext Loss-free tensile ductility of dual-structure titanium composites via an interdiffusion and self-organization strategy

Liu L, Li S, Pan D, Hui D, Zhang X, Li B, et al.

Proc Natl Acad Sci U S A, 2023 Jul 11;120(28):e2302234120.
PMID: 37399391 DOI: 10.1073/pnas.2302234120

The deformation-coordination ability between ductile metal and brittle dispersive ceramic particles is poor, which means that an improvement in strength will inevitably sacrifice ductility in dispersion-strengthened metallic materials. Here, we present an inspired strategy for developing dual-structure-based titanium matrix composites (TMCs) that achieve 12.0% elongation comparable to the matrix Ti6Al4V alloys and enhanced strength compared to homostructure composites. The proposed dual-structure comprises a primary structure, namely, a TiB whisker-rich region engendered fine grain Ti6Al4V matrix with a three-dimensional micropellet architecture (3D-MPA), and an overall structure consisting of evenly distributed 3D-MPA "reinforcements" and a TiBw-lean titanium matrix. The dual structure presents a spatially heterogeneous grain distribution with 5.8 μm fine grains and 42.3 μm coarse grains, which exhibits excellent hetero-deformation-induced (HDI) hardening and achieves a 5.8% ductility. Interestingly, the 3D-MPA "reinforcements" show 11.1% isotropic deformability and 66% dislocation storage, which endows the TMCs with good strength and loss-free ductility. Our enlightening method uses an interdiffusion and self-organization strategy based on powder metallurgy to enable metal matrix composites with the heterostructure of the matrix and the configuration of reinforcement to address the strength-ductility trade-off dilemma.
Extensive peritoneal lavage with saline after curative gastrectomy for gastric cancer (EXPEL): a multicentre randomised controlled trial

Yang HK, Ji J, Han SU, Terashima M, Li G, Kim HH, et al.

Lancet Gastroenterol Hepatol, 2021 02;6(2):120-127.
PMID: 33253659 DOI: 10.1016/S2468-1253(20)30315-0

BACKGROUND: Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Early studies suggest that extensive intraoperative peritoneal lavage (EIPL) might reduce the risk of peritoneal recurrence and improve survival. We aimed to evaluate the survival benefit of EIPL in patients with gastric cancer undergoing curative gastrectomy.
METHODS: In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres from South Korea, China, Japan, Malaysia, Hong Kong, and Singapore. Patients were randomly assigned to receive surgery and EIPL (EIPL group) or surgery alone (standard surgery group) via a web-based programme in random permuted blocks in varying block sizes of four and six, assuming equal allocation between treatment groups. Randomisation was stratified according to study site and the sequence was generated using a computer program and concealed until the interventions were assigned. After surgery in the EIPL group, peritoneal lavage was done with 1 L of warm (42°C) normal 0·9% saline followed by complete aspiration; this procedure was repeated ten times. The primary endpoint was overall survival. All analyses were done assuming intention to treat. This trial is registered with ClinicalTrials.gov, NCT02140034.
FINDINGS: Between Sept 16, 2012, and Aug 3, 2018, 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402). Two patients in the EIPL group and one in the standard surgery group withdrew from the trial immediately after randomisation and were excluded from the intention-to-treat analysis. At the third interim analysis on Aug 28, 2019, the predictive probability of overall survival being significantly higher in the EIPL group was less than 0·5%; therefore, the trial was terminated on the basis of futility. With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62). 3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group. 60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. The most common adverse events included anastomotic leak (ten [3%] of 346 patients in the EIPL group vs six [2%] of 362 patients in the standard surgery group), bleeding (six [2%] vs six [2%]), intra-abdominal abscess (four [1%] vs five [1%]), superficial wound infection (seven [2%] vs one [<1%]), and abnormal liver function (six [2%] vs one [<1%]). Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death.
INTERPRETATION: EIPL and surgery did not have a survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for gastric cancer.
FUNDING: National Medical Research Council, Singapore.
Fulltext Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Mózes FE, Lee JA, Vali Y, Alzoubi O, Staufer K, Trauner M, et al.

Lancet Gastroenterol Hepatol, 2023 Aug;8(8):704-713.
PMID: 37290471 DOI: 10.1016/S2468-1253(23)00141-3

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.
METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.
FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.
INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
FUNDING: Innovative Medicines Initiative 2.
Precessing jet nozzle connecting to a spinning black hole in M87

Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.

Nature, 2023 Sep;621(7980):711-715.
PMID: 37758892 DOI: 10.1038/s41586-023-06479-6

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

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