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The [Fe]/H 2 O 2 oxidation system has found wide applications in chemistry and biology. Halogenation with this [Fe]/H 2 O 2 oxidation protocol and halide (X - ) in the biological system is well established with the identification of heme-iron-dependent haloperoxidases. However, mimicking such halogenation process is rarely explored for practical use in organic synthesis. Here, we report the development of a nonheme iron catalyst that mimics the heme-iron-dependent haloperoxidases to catalyze the generation of HOBr from H 2 O 2 /Br - with high efficiency. We discovered that a tridentate terpyridine (TPY) ligand designed for Fenton chemistry was optimal for FeBr 3 to form a stable nonheme iron catalyst [Fe(TPY)Br 3 ], which catalyzed arene bromination, Hunsdiecker-type decarboxylative bromination, bromolactonization, and oxidation of sulfides and thiols. Mechanistic studies revealed that Fenton chemistry ([Fe]/H 2 O 2 ) might operate to generate hydroxyl radical (HO • ), which oxidize bromide ion [Br - ] into reactive HOBr. This nonheme iron catalyst represents a biomimetic model for heme-iron-dependent haloperoxidases with potential applications in organic synthesis, drug discovery, and biology.

The excessive CO 2 emission has gained global attentions due to its potential effects on climate change, plant nutrition deterioration, and human health and safety. Metal-organic frameworks (MOFs) featured with high specific surface area, adjustable pore size, and tailorable morphology have been widely applied for CO 2 capture. However, some drawbacks of poor mechanical stability and uneven distribution of mesopores limit their further applications. Herein, we demonstrate a one-step synthesis of bimetallic center framework (OSSBCF) and pore reconstruction (PRC) strategy to prepare the hierarchical porous Zn/Co-ZIF@ANF aerogels. This unique design achieves the construction of efficient gas transfer channels and creates massive micropores with abundant Lewis basic adsorption sites. Benefiting from theses merits, the bimetallic Zn/Co-ZIF@ANF aerogels demonstrate high MOFs loading mass of 47.51 wt%, high specific surface area of 686.39 m 2 g -1 , and large porosity of 99.31 %. Moreover, the bimetallic Zn/Co-ZIF@ANF aerogels exhibit an enhanced CO 2 adsorption capacity of 5.99 mmol/g and CO 2 /N 2 adsorption selectivity of 35 at 25 °C and 1 bar. The CO 2 capacity of bimetallic Zn/Co-ZIF@ANF aerogels keep up to 95.19 % after ten cycles of CO 2 adsorption, indicating the excellent long-term recycle stability. Therefore, this study provides a promising strategy to engineer hierarchical porous bimetallic MOF aerogels toward practical CO 2 capture., 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 © 2024 Elsevier Inc. All rights reserved.)

Objectives: To assess the feasibility and accuracy of a new prototype robotic implant system for the placement of zygomatic implants in edentulous maxillary models., Methods: The study was carried out on eight plastic models. Cone beam computed tomographs were captured for each model to plan the positions of zygomatic implants. The hand-eye calibration technique was used to register the dynamic navigation system to the robotic spaces. A total of 16 zygomatic implants were placed, equally distributed between the anterior and the posterior parts of the zygoma. The placement of the implants (ZYGAN®, Southern Implants) was carried out using an active six-jointed robotic arm (UR3e, Universal Robots) guided by the dynamic navigation coordinate transformation matrix. The accuracy of the implant placement was assessed using EvaluNav and GeoMagicDesignX® software based on pre- and post-operative CBCT superimposition. Descriptive statistics for the implant deviations and Pearson's correlation analysis of these deviations to force feedback recorded by the robotic arm were conducted., Results: The 3D deviations at the entry and exit points were 1.80 ± 0.96 mm and 2.80 ± 0.95 mm, respectively. The angular deviation was 1.74 ± 0.92°. The overall registration time was 23.8 ± 7.0 min for each side of the model. Operative time excluding registration was 66.8 ± 8.8 min for each trajectory. The exit point and angular deviations of the implants were positively correlated with the drilling force perpendicular to the long axis of the handpiece and negatively correlated with the drilling force parallel to the long axis of the handpiece., Conclusion: The errors of the dynamic navigation-guided robotic placement of zygomatic implants were within the clinically acceptable limits. Further refinements are required to facilitate the clinical application of the tested integrated robotic-dynamic navigation system., Clinical Significance: Robotic placement of zygomatic implants has the potential to produce a highly predictable outcome irrespective of the operator's surgical experience or fatigue. The presented study paves the way for clinical applications., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The growth of the Internet of Things has focused attention on visualized sensors as a key technology. However, it remains challenging to achieve high sensing accuracy and self-power ability. Here, we propose a self-powered visualized tactile-acoustic sensor (SVTAS) based on an elaborated triboelectrification-induced electroluminescence (TIEL) unit. To date, it features a high brightness of 0.5 mW cm -2 (32 cd m -2 ) and a record-low detection limit of 0.5 kPa in horizontal-sliding mode. Meanwhile, the SVTAS is applicable to convert acoustic waves into TIEL signals in contact-separation mode, showing the highest response to the 44.07 Hz sound, a high signal-to-noise ratio of 8.7 dB -1 , and an ultrafast response time of 0.8 ms. Furthermore, advanced artificial visualized perception systems are constructed with excellent performance in recognizing motion trajectories and human speech with different words/sentences. This work paves the way for the highly efficient and sustainable development of new-generation self-powered visualized perception systems, contributing a solution to wireless communication free from electromagnetic interference.

Zinc (Zn) deficiency is a significant nutritional limitation to crop yield globally, particularly in calcareous soil environments. Tree peony of Peaonia ostii 'Fengdan' is regarded as an oil crop due to its seeds rich in alpha-linolenic acid, a beneficial compound for health promotion. However, low seed yield remains a primary challenge in attaining sufficient seed oil from tree peony. In this study, Zn fertilization was applied to soil or foliage of P. ostii 'Fengdan' in the growth period before fruit development. Our findings reveal that foliar Zn-spraying, as opposed to soil application, proves to be a more effective method for augmenting seed yield, Zn accumulation and photosynthetic capacity in 'Fengdan'. Comparative analyses of the leaf proteome of 'Fengdan' using iTRAQ profiling under foliar Zn-spraying identified 115 differentially expressed proteins (DEPs), including 36 upregulated proteins, which likely contribute to the observed increase in seed yields of 'Fengdan' caused by foliage Zn-spraying. Specifically, Zn 2+ stimulation of phosphatidylinositol signaling initiates a cascade of metabolic regulations. Firstly, ATP synthesis promotes leaf photosynthetic capacity, facilitated by improved sucrose metabolism through upregulated pullulanase and 1,4-alpha-glucan-branching enzyme. Furthermore, lipid synthesis and transport are facilitated by upregulated lipoyl synthase and plastid lipid-associated proteins. Additionally, DEPs involved in secondary metabolism are upregulated in the production of various metabolites conducive to 'Fengdan' growth. Overall, our results demonstrate that foliage Zn-spraying enhances seed yield in P. ostii 'Fengdan' by elevating Zn content and secondary metabolite synthesis in leaves, thereby augmenting leaf photosynthetic capacity and lipid synthesis. This study provides an effective way to increase seed yield of tree peony by exogenous Zn application., 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 © 2024 Elsevier Masson SAS. All rights reserved.)

MicroRNAs (miRNAs) play pivotal roles in gene regulation and their dysregulation is implicated in various diseases, including cancer. Current methods for miRNA analysis often involve complex procedures and high costs, limiting their clinical utility. Therefore, there is a critical need for the development of simpler and more cost-effective miRNA detection techniques to enable early disease diagnosis. In this study, we introduce a novel one-enzyme for miRNA one-step detection method using Taq DNA polymerase, termed OSMOS-qPCR. We optimized the PCR buffer, PCR program, Taq DNA Polymerase concentrations and reverse PCR primer concentrations, resulted in a wide linear range from 100 fM to 0.001 fM (R 2  > 0.98 for each miRNA), the detection limit for OSMOS-qPCR was 0.0025 fM. Furthermore, OSMOS-qPCR demonstrates excellent specificity to differentiation of less than 0.1 % nonspecific signal. Finally, we demonstrated the robust amplification efficiency, enabling the detection of trace amounts of cell-free miRNA in serum samples, and the excellent discrimination ability between gastrointestinal cancers and control subjects (AUC value = 1.0) if combined two miRNAs. The development of OSMOS-qPCR offering a simpler, cost-effective, and efficient detection method, has the potential to be non-invasive strategy for early detection of gastrointestinal cancers., 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 © 2024 Elsevier B.V. All rights reserved.)

Recent studies have shown that ultrashort plasma cell-free DNA (uscfDNA), a novel type of cfDNA fragment approximately 50 nucleotides long, differs from conventional monocyte-derived cfDNA in several aspects, including specific extraction requirements and a higher incidence of tumor-specific genetic alterations. uscfDNA shows promise in enhancing liquid biopsy sensitivity for cancer detection, with distinct methylation profiles observed in cancer patients. These findings suggest uscfDNA analysis could significantly improve non-invasive cancer diagnostics, offering new avenues for early detection and personalized medicine strategies., Competing Interests: None., (AJCEI Copyright © 2024.)

Background: Recent research underscores the pivotal role of immune checkpoints as biomarkers in colorectal cancer (CRC) therapy, highlighting the dynamics of resistance and response to immune checkpoint inhibitors. The impact of epigenetic alterations in CRC, particularly in relation to immune therapy resistance, is not fully understood., Methods: We integrated a comprehensive dataset encompassing TCGA-COAD, TCGA-READ, and multiple GEO series (GSE14333, GSE37892, GSE41258), along with key epigenetic datasets (TCGA-COAD, TCGA-READ, GSE77718). Hierarchical clustering, based on Euclidean distance and Ward's method, was applied to 330 primary tumor samples to identify distinct clusters. The immune microenvironment was assessed using MCPcounter. Machine learning algorithms were employed to predict DNA methylation patterns and their functional enrichment, in addition to transcriptome expression analysis. Genomic mutation profiles and treatment response assessments were also conducted., Results: Our analysis delineated a specific tumor cluster with CpG Island (CGI) methylation, termed the Demethylated Phenotype (DMP). DMP was associated with metabolic pathways such as oxidative phosphorylation, implicating increased ATP production efficiency in mitochondria, which contributes to tumor aggressiveness. Furthermore, DMP showed activation of the Myc target pathway, known for tumor immune suppression, and exhibited downregulation in key immune-related pathways, suggesting a tumor microenvironment characterized by diminished immunity and increased fibroblast infiltration. Six potential therapeutic agents-lapatinib, RDEA119, WH.4.023, MG.132, PD.0325901, and AZ628-were identified as effective for the DMP subtype., Conclusion: This study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies., (© 2024. Springer Nature Switzerland AG.)

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al 2 O 3 ) and the effects of four oxides (SiO 2 , Al 2 O 3 , Fe 2 O 3 , and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al 2 O 3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al 2 O 3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO 2 was better for the reduction of Na 2 CrO 4 and K 2 CrO 4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO 4 decomposed above 700°C to form MgCr 2 O 4 , and the reaction between MgCrO 4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl 3 , it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO 2 , Al 2 O 3 , and Fe 2 O 3 , which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment., 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. Published by Elsevier B.V.)

High temperature stress has long-term negative effects on the growth and development of silkworm (Bombyx mori). Different silkworm varieties show the different tolerance to high temperature. The induction of autophagy is linked to increased thermotolerance in diverse ectothermic organisms. However, the function of autophagy in the thermotolerant and thermosensitive silkworm strains under high-temperature conditions remains unclear. The thermotolerant Liangguang NO.2 and thermosensitive Jingsong × Haoyue strains were used to explore the role of autophagy in thermotolerance. Here, we first found that the larval body weight gain was increased in the thermosensitive Jingsong × Haoyue strain, but there was no difference in the thermotolerant Liangguang NO.2 strain under high temperature conditions. High temperature stress had a negative influence on the cocoon performance in both the Liangguang NO.2 and Jingsong × Haoyue strains. Additionally, the autophagy-related gene Atg5 mRNA expression in the Liangguang NO.2 strain was upregulated by high temperature, while the expression of Atg12 mRNA was reduced in the Jingsong × Haoyue strain. Titers of 20-Hydroxyecdysone and the ultraspiracle 1 mRNA expression in the Liangguang NO.2 strain were upregulated by high temperature, which might be associated with the induction of autophagy. These results demonstrate the potentially regulatory mechanism of autophagy in silkworms' tolerance to high temperature, providing a theoretical basis for exploring the physiological mechanism of thermotolerance in insects., (© 2024 Wiley Periodicals LLC.)

Lithium (Li) metal is regarded as the most desirable anode candidates for high-energy-density batteries by virtue of its lowest redox potential and ultrahigh theoretical specific capacity. However, uncontrollable Li dendritic growth, infinite volume variation and unstable solid electrolyte interface (SEI) ineluctably plague its commercialization process. Herein, the three-dimensional (3D) nanofiber functional layers with synergistic soft-rigid feature, consisting of tin oxide (SnO 2 )-anchored polyvinylidene fluoride (PVDF) nanofibers, are directly electrospun on copper current collector. This strategy can effectively regulate uniform Li deposition and strengthen SEI stability through the dual effect of physical accommodation and chemical ionic intervention. On the one hand, the nanofiber interlayers with excellent electrolyte affinity and well-distributed Li + transport pathways can promote uniform Li + flux distribution and large-size Li deposition. On the other hand, the rigid SnO 2 contributes to reducing Li nucleation overpotential and stabilizing SEI layer assisted by its spontaneous reaction with Li. As a result, the smooth and dense Li deposition is achieved by such soft-rigid nanofiber interlayers, thereby extending the cycling life and improving the safety application of Li metal batteries. This work offers a new route for efficient protection of Li metal anodes and brings a new inspiration for developing high-energy-density Li metal batteries., 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 © 2024 Elsevier Inc. All rights reserved.)

Stretchable organic transistors for skin-like biomedical applications require low-voltage operation to accommodate limited power supply and safe concerns. However, most of the currently reported stretchable organic transistors operate at relatively high voltages. Decreasing their operational voltage while keeping the high mobility still remains a key challenge. Here, the study presents a new dielectric design to achieve high-dielectric constant poly(urea-urethane) (PUU) elastomer, by incorporating a flexible small-molecular diamine crosslinking agent 4-aminophenyl disulfide (APDS) into the main chain of (poly (propylene glycol), tolylene 2,4-diiso-cyanate terminated) (PPG-TDI). Compared with commercial elastomers, the PUU elastomer as dielectric of the stretchable organic transistors shows the outstanding advantages including lower surface roughness (0.33 nm), higher adhesion (45.18 nN), higher dielectric constant (13.5), as well as higher stretchability (896%). The PUU dielectric enables the intrinsically stretchable, all-solution-processed organic transistor to operate at a low operational voltage down to -10 V, while preserving a substantial mobility of 1.39 cm 2  V -1  s -1 . Impressively, the transistor also demonstrates excellent electrical stability under repeated switching of 10 000 cycles, and remarkable mechanical robustness when stretched up to 100%. The work opens up a new molecular engineering strategy to successfully realize low-voltage high-mobility stretchable all-solution-processed organic transistors., (© 2024 Wiley‐VCH GmbH.)

Objective: To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV)., Methods: A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA)., Results: Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29 (34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance., Conclusion: NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.

Here a mechanism for self-compression of laser pulses is presented, based on period density-modulated plasma. In this setup, two pump beams intersect at a small angle within the plasma. This interaction is facilitated by the ponderomotive ion mechanism, which causes a modulation in the density of plasma with long wavelengths and low amplitude. This modulation enhances the backward Raman scattering of the probe pulse. The trailing edge of the probe experiences greater energy loss, resulting in a steeper intensity gradient. This, in turn, induces an asymmetric self-phase modulation, which elevates the instantaneous frequency. It is notable that the laser in plasma exhibits opposite group velocity dispersion compared to traditional solid-state media. This unique property allows laser pulses to undergo dispersion compensation while broadening the spectrum, ultimately leading to self-compression. The 2D-PIC simulations demonstrate these phenomena, highlighting how period density-modulated plasma contributes to an asymmetric spectral distribution. The intricate interplay among self-phase modulation, group velocity, and backward Raman scattering results in the self-compressing of the laser pulse. Specifically, the pulses are compressed from their Fourier transform limit duration of 50 fs to a significantly reduced duration of 8 fs at plasma densities below 1/4 critical density, without the transverse self-focusing effects.

Background: DNA methylation is highly correlated with cancer and embryo development, and plasma-based methylation markers have been widely used for cancer early detection. However, whether the commonly used cancer methylation markers cause "false positives" in the plasma of pregnant women has not been comprehensively evaluated., Methods: We conducted a case-control study from February 2021 to March 2023, which included 138 pregnant women and 44 control women. Plasma cell-free DNA (cfDNA) was isolated and bisulfite-converted, and then the methylation levels of eight methylated markers related to gastrointestinal cancer (SEPT9, SDC2, C9orf50, KCNQ5, CLIP4, TFPI2, ELMO1 and ZNF582) and three markers related to lung cancer (SHOX2, RASSF1A and PTGER4) were analyzed., Results: When comparing the plasma of pregnant women to that of control women, SEPT9, CLIP4, ZNF582, SHOX2, RASSF1A and PTGER showed significantly higher levels of methylation (p < 0.05). These positive signals originate from the placenta/fetus rather than the mother. We found no discernible difference in DNA methylation levels between fetal cfDNA fractions of < 10 % and ≥ 10 % in pregnant women (p > 0.05), while CLIP4 and PTGER4 showed high methylation levels in the assisted fertilization group compared to the natural fertilization group (p < 0.05)., Conclusion: Our study shows that cancer and fetus/placenta exhibit similar DNA methylation patterns, and some gastrointestinal cancer and lung cancer-related methylation markers also show positives in maternal plasma. This is an important consideration in the design and application of plasma-based cancer liquid biopsy assays., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection., Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening., Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma., Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC., Competing Interests: All 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 Xu, Wang, Pei, Wang, Xue and Zhao.)

Introduction: Cryopreservation of semen can give full play to the reproductive advantages of male animals. However, in actual production, due to the poor frost resistance of sheep semen and the low conception rate, the promotion of sheep frozen semen is greatly hindered. Therefore, it is urgent to improve the frost resistance of semen to improve the quality of frozen semen. At present, most studies on improving the quality of frozen semen are based on the improvement of semen dilutions, and few studies on improving the freezing resistance of ram semen by feeding functional amino acids., Methods: Therefore, 24 Turpan black rams were divided into high antifreeze group (HF) and a low antifreeze group (LF) Each of these groups was further randomly divided into control and experimental subgroups. The control subgroup was fed a basal diet, while the experimental subgroup received an additional 12 g/d of L -Cit supplementation based on the control group for a duration of 90 days., Results: The results showed that Following L -Cit supplementation, the experimental group demonstrated significantly elevated sperm density and VSL (Velocity of straight line), T-AOC, GSH-Px, and NO levels in fresh semen compared to the control group ( P < 0.01). After thawing, the experimental group exhibited significantly higher levels of T-AOC, GSH-Px, and NO compared to the control group ( P < 0.01). Additionally, the HFT group, after thawing frozen semen, displayed significantly higher HK1 protein expression compared to the control group. The number of spermatogonia, spermatocytes, and sperm cells in the HFT group was significantly higher than that in the HFC group. Moreover, 16S rRNA sequence analysis showed that Candidatus&#95;Saccharimonas, Staphylococcus, Weissella, succinivbrionaceae&#95;UcG&#95;002 , and Quinella were significantly enriched in the rumen of the HFT group, while Ureaplasma was significantly enriched in the HFC group. In the duodenum, Clostridiales&#95;bacterium&#95;Firm&#95;14, Butyrivibrio , and Prevotellaceae&#95;NK3831&#95;group were significantly enriched in the HFT group, whereas Desulfovibrio and Quinella were significantly enriched in the HFC group., Discussion: Under the conditions employed in this study, L -Cit supplementation was found to enhance the intestinal flora composition in rams, thereby improving semen quality, enhancing the antifreeze performance of semen, and promoting the development of testicular spermatogenic cells., 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 Fan, Aihemaiti, Fan, Dilixiati, Zhao, Li, Chen and Zhao.)

Background: The flexibility of the robotic system in resection and reconstruction provides potential benefits in pancreaticoduodenectomy. Increasingly, robotic pancreaticoduodenectomy (RPD) has been reported with favourable outcomes, but high-level evidence is still scarce. We aimed to compare the short-term postoperative outcomes of RPD with those of open pancreaticoduodenectomy (OPD), and hypothesised that postoperative length of hospital stay would be shorter after RPD than after OPD., Methods: This multicentre, open-label randomised controlled trial was conducted at three high-volume hospitals in China. Patients were considered for participation in this trial if they were aged 18-75 years, had a resectable benign, premalignant, or malignant tumour in the pancreatic head or periampullary region; and were suitable for both RPD and OPD. Patients with distant metastases were excluded. Block randomisation was done with random block sizes of four, stratified by centre. Allocation was concealed via individual, sequentially numbered, opaque sealed envelopes. Eligible patients were randomly assigned to the RPD group or the OPD group in a 1:1 ratio by a masked research assistant. Surgeons and patients were not masked to trial group, but data collectors, postoperative outcome assessors, and data analysts were. All patients underwent RPD or OPD according to previously reported techniques. Participating surgeons had surpassed the learning curves of at least 40 RPD and 60 OPD procedures. The primary outcome was postoperative length of hospital stay, which was analysed in the modified intention-to-treat (mITT) population. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2200056809) and is complete., Findings: Between March 5 and Dec 20, 2022, 292 patients were screened for eligibility, of whom 164 were enrolled and randomly assigned to the RPD group (n=82) or the OPD group (n=82). 161 patients who underwent surgical resection were included in the mITT analysis (81 in the RPD group and 80 in the OPD group). 94 (58%) participants were male and 67 (42%) were female. Postoperative length of hospital stay was significantly shorter in the RPD group than in the OPD group (median 11·0 days [IQR 9·0 to 19·5] vs 13·5 days [11·5 to 18·0]; median difference -2·0 [95% CI -4·0 to 0·0]; p=0·029). During a follow-up period of 90 days, six (7%) of 81 patients in the RPD group and five (6%) of 80 patients in the OPD group required readmission. Reasons for readmission were intra-abdominal haemorrhage (one in each group), vomiting (two in the RPD group and one in the OPD group), electrolyte disturbance (one in each group), and fever (two in each group). There were two (1%) in-hospital deaths within 90 days of surgery, one in each group. The postoperative 90-day mortality rate (difference -0·02% [-5·6 to 5·5]; p=1·00) and the incidence of severe complications (ie, Clavien-Dindo grade ≥3; difference -1·5% [-14·5 to 11·4]; p=0·82) were similar between the two groups., Interpretation: For surgeons who had passed the learning curve, RPD was safe and feasible with the advantage of shorter postoperative length of hospital stay than OPD. Future research should focus on the medium-term and long-term outcomes between RPD and OPD., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

MicroRNAs (miRNAs) are increasingly recognized as promising biomarkers for early disease diagnosis and prognosis. Therefore, the need for rapid, robust methods for multiplex miRNA detection in biological research and clinical diagnosis is crucial. This study introduces a novel multiplex miRNA detection method, SMOS-qPCR (Sensitive and Multiplexed One-Step RT-qPCR). The method integrates multiplexed reverse transcription and TaqMan-based qPCR into a single tube, employing a one-step operation on a real-time PCR system. We investigated the effect of 3' end phosphorylation of the Linker, Linker concentration and probe concentration on the SMOS-qPCR, resulted in a wide linear range from 1 fM to 0.1 zM (R 2  ≥ 0.99 for each miRNA), surpassing the capabilities of stem-loop RT-qPCR and SYBR Green One-step RT-qPCR. The method showed excellent performance in distinguishing mature miRNA from miRNA precursor, and successfully detected four miRNAs in a single tube without cross-interference. Its high specificity enables precise differentiation of less than 1% nonspecific signal. Finally, we demonstrated the effectiveness of the SMOS-qPCR system in detecting circulating miRNAs in serum samples, distinguishing between esophageal cancers and health individuals with high AUC values (>0.940). In conclusion, the proposed SMOS-qPCR system offers a straightforward and promising approach for miRNA profiling in future clinical applications., Competing Interests: Declaration of competing interest Authors Guodong Zhao, Kai Wang and Xiaoyu Liu are employed by Suzhou VersaBio Technologies 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 © 2023 Elsevier B.V. All rights reserved.)

Vitrification is a crucial method for preserving animal germ cells. Considering the increased oxidative stress and organelle damage incurred, it is still necessary to make the process more efficient for oocytes. As the energy source of oocytes, mitochondria are the most abundant organelle in oocytes and play a crucial role in their maturation. Here, we found that Mito-TEMPO, a mitochondria-targeted antioxidant, could efficaciously improve the oxidative stress injury of vitrified oocytes by recovering mitochondrial function via the mitochondrial respiratory chain. It was observed that Mito-TEMPO not only improves oocyte viability and meiosis but also maintains spindle structure. A subsequent study indicated that Mito-TEMPO effectively rescued mitochondrial dysfunction and attenuated vitrification-induced oxidative stress. Further investigation revealed that Mito-TEMPO regulates vitrified oocytes' intracellular Ca 2+ homeostasis and ATP content and provides strong antioxidant properties. Additionally, an analysis of the transcriptome at the single-cell level revealed that the respiratory chain mediates the beneficial effect of Mito-TEMPO on vitrified oocytes. Overall, our findings indicate that supplementing oocytes with Mito-TEMPO is an effective method to shield them from the damage caused by vitrification. In addition, the beneficial effects of Mito-TEMPO on vitrified sheep oocytes could inspire further investigations of the principles underlying oocyte cryobiology in other animals.

Trehalose is a non-reducing disaccharide and participates in physiological activities such as organ formation, energy metabolism, and stress resistance in insects. The Bmtret 1 gene family is mainly involved in in the sugar metabolism of silkworm. In the present study, phylogenetic analysis divided 21 Bmtret 1 orthologs into three clades. These genes are equally distributed on the nine chromosomes. The cis-elements in the promoter regions of Bmtret 1s indicated the possible function of Bmtret 1s in response to hormones and environmental stimulus. The qPCR analysis showed the significantly different expression levels of Bmtret 1s in different tissues and organs, indicating possible functional divergence. In addition, most Bmtret 1s showed disturbed expression levels in response to silkworm nuclear polyhedrosis virus (BmNPV) stresses. Our results provide a clue for further functional dissection of the Tret 1s in Bombyx mori and implicate them as potential regulators of antiviral responses.

Nosema bombycis, an obligate intracellular parasite, is a single-celled eukaryote known to infect various tissues of silkworms, leading to the manifestation of pebrine. Trehalase, a glycosidase responsible for catalyzing the hydrolysis of trehalose into two glucose molecules, assumes a crucial role in thermal stress tolerance, dehydration, desiccation stress, and asexual development. Despite its recognized importance in these processes, the specific role of trehalase in N. bombycis remains uncertain. This investigation focused on exploring the functions of trehalase 3 in N. bombycis (NbTre3). Immunofluorescence analysis of mature (dormant) spores indicated that NbTre3 primarily localizes to the spore membrane or spore wall, suggesting a potential involvement in spore germination. Reverse transcription-quantitative polymerase chain reaction results indicated that the transcriptional level of NbTre3 peaked at 6 h post N. bombycis infection, potentially contributing to energy storage for proliferation. Throughout the life cycle of N. bombycis within the host cell, NbTre3 was detected in sporoplasm during the proliferative stage rather than the sporulation stage. RNA interference experiments revealed a substantial decrease in the relative transcriptional level of NbTre3, accompanied by a certain reduction in the relative transcriptional level of Nb16S rRNA. These outcomes suggest that NbTre3 may play a role in the proliferation of N. bombycis. The application of the His pull-down technique identified 28 proteins interacting with NbTre3, predominantly originating from the host silkworm. This finding implies that NbTre3 may participate in the metabolism of the host cell, potentially utilizing the host cell's energy resources., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Excessive CO 2 emissions and the resultant global warming present significant environmental challenges, posing threats to human health and public safety. Metal-organic frameworks (MOFs), known for their high specific area and large porosity, hold the promise for CO 2 capture. However, a major obstacle is the low loading mass of MOFs and the limited interface affinity and compatibility between MOFs and substrates. In this study, we present an electrospinning-assisted in-situ synthesis dual metallic framework strategy for preparing flexible Zn/Co-ZIF nanofibrous membranes (NFMs). This method achieves the high loading mass of MOFs and introduces abundant Lewis basic sites, thereby enhancing the CO 2 adsorption. The dual metallic Zn/Co-ZIF NFMs exhibit remarkable features, including high MOF loading mass (70.23 wt%), high specific surface area (379.63 m 2 g -1 ), large porosity (92.34 %), high CO 2 adsorption capacity (4.43 mmol/g), high CO 2 /N 2 adsorption selectivity (37), and high CO 2 /CH 4 adsorption selectivity (31). Moreover, the dual metallic Zn/Co-ZIF NFMs demonstrate robust structural stability and durability attributed to the excellent interface affinity between MOFs and NFMs, retaining 96.56 % of their initial capacity after 10 adsorption-desorption cycles. This work presents a prospective direction for developing flexible dual metallic MOF NFMs for the efficient capture of CO 2 ., 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 Inc. All rights reserved.)

Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs., Methods: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers., Results: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively)., Conclusion: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs., Competing Interests: Declaration of Competing Interest Authors Guodong Zhao, Lishuang Song, Kai Wang and Shangmin Xiong are employed by Suzhou VersaBio Technologies 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tree peony (Paeonia sect. Moutan DC.) is a famous flower native to China with high ornamental, medicinal, and oil value. However, the low regeneration rate of callus is one of the main constraints for the establishment of a genetic transformation system in tree peony. By histomorphological observation, transcriptomic analysis and metabolite determination, we investigated the molecular mechanism of somatic embryogenesis after the establishment of a culture system and the induction of somatic embryo(SE) formation., Results: We found that SE formation was successfully induced when cotyledons were used as explants. A total of 3185 differentially expressed genes were screened by comparative transcriptomic analysis of embryogenic callus (EC), SE, and non-embryogenic callus (NEC). Compared to NEC, the auxin synthesis-related genes GH3.6 and PCO2 were up-regulated, whereas cytokinin dehydrogenase (CKX6) and CYP450 family genes were down-regulated in somatic embryogenesis. In SE, the auxin content was significantly higher than the cytokinin content. The methyltransferase-related gene S-adenosylmethionine synthase (SAMS) and the flavonoid biosynthesis-related gene (ANS and F3'5'H) were down-regulated in somatic embryogenesis. The determination of flavonoids showed that rhoifolin and hyperoside had the highest content in SE. The results of transcriptome analysis were consistent with the relative expression of 8 candidate genes by quantitative polymerase chain reaction analysis., Conclusion: The results revealed that auxin and cytokinin may play a key role in 'Fengdan' somatic embryogenesis. The genes related to somatic embryogenesis were revealed, which has partly elucidated the molecular mechanism of somatic embryogenesis in 'Fengdan'., (© 2023. The Author(s).)

Context: Treatment failure due to multidrug resistance (MDR) is a crucial hurdle during chemotherapy. MDR is generally correlated with an upregulation of adenosine triphosphate (ATP)-binding cassette (ABC) transport proteins. Also, aberrant activation of the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway can counteract chemotherapeutic induction. Identification of safe and functioning MDR-reversing compounds is necessary in gastric-cancer therapy., Objective: The study intended to examine the role of Quercetin (Qur) in the mediation of osmotic glycoprotein (P-gp) expression and activity as an ABC transporter in the PI3K/Akt/ P-gp cascade in the oxaliplatin (OxR)-resistant, gastric-cancer cell line KATOIII/OxR., Design: The research team performed a laboratory study., Setting: The study took place at Nantong Haimen People's Hospital., Outcome Measures: The research team: (1) determined the impact of OxR on cell viability after treatment with Qur using trypan blue and "3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide" (MTT) assays; (2) employed a rhodamine 123 (Rh123) assay to detect the activity of P-gp; (3) used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to measure mRNA expression of P-gp; and (4) detected apoptosis using an enzyme-linked immunoassay (ELISA) cell-death assay., Results: Qur: (1) increased the cytotoxicity of OxR; (2) downregulated the expression level and activity of P-gp and reversed MDR through the enhancement of the cytotoxicity of intracellular OxR in KATOIII/OxR cells; and (3) enhanced the apoptosis rate in KATOIII/OxR cells., Conclusions: Qur induced a dramatic reduction in the survival rate of KATOIII/OxR cells and may reverse OxR resistance through a decrease in P-gp expression and activity. These data imply that exposure of KATOIII/OxR cells in the dose-dependent manner to Qur can circumvent MDR by improving the intracellular accumulation of OxR. Qur might provide a new treatment strategy and improve patients' survival after chemotherapy for gastric cancer.

Background: Recently, the antioxidant properties of the natural compound, selenomethionine (Se-Met), have been recognized. However, its effect on the osteogenic mineralization of the Wnt/β-Catenin pathway under conditions of oxidative stress and inflammation remain unclear., Methods: This study utilized tert -butyl hydroperoxide (TBHP) to simulate oxidative stress and inflammation. Se-Met was then subsequently used to inhibit these effects in vitro ., Results: TBHP induces oxidative stress and inflammatory responses by increasing the expression of reactive oxygen species and NLRP3, whereas decreasing the expression of GPX4, thereby inhibiting the viability of MC3T3-E1 cells. TBHP further promotes lipid peroxidation and damages the ultrastructure of mitochondria. Furthermore, TBHP inhibits the expression levels of β-Catenin, thereby reducing the activity of the Wnt pathway, which in turn suppresses the osteogenic differentiation and mineralization capacity. Importantly, Se-Met significantly alters the aforementioned responses to enhance expression levels of Wnt pathway-related proteins and improving the osteogenic differentiation and mineralization capacity of the cells., Conclusion: Se-Met enhances antioxidant and anti-inflammatory responses in MC3T3-E1 cells via the Wnt/β-Catenin signaling pathway to promote osteogenesis. Thus, Se-Met plays a crucial role in the field of bone homeostasis, and presents an opportunity for the future development of novel drugs for treating osteoporosis and maintaining bone stability. However, further detailed preclinical animal studies are required to generate solid and reliable data to aid this development., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background: Esophageal cancer (EC) is a leading cause of cancer-related deaths in China, with the 5-year survival rate reaching less than 30%, because most cases were diagnosed and treated at the advanced stage. However, there is still a lack of low-cost, efficient, and accurate non-invasive methods for the early detection of EC at present. Methods: A total of 48 EC plasma and 101 control plasma samples were collected in a training cohort from 1 January 2021 to 31 December 2021, and seven cancer-related DNA methylation markers ( ELMO1 , ZNF582 , FAM19A4 , PAX1 , C13orf18 , JAM3 and TERT ) were tested in these samples to select potential markers. In total, 20 EC, 10 gastric cancer (GC), 10 colorectal cancer (CRC), and 20 control plasma samples were collected in a validation cohort to evaluate the two-gene panel. Results: ZNF582 , FAM19A4 , JAM3 , or TERT methylation in plasma was shown to significantly distinguish EC and control subjects ( p < 0.05), and the combination of ZNF582 and FAM19A4 methylation was the two-gene panel that exhibited the best performance for the detection of EC with 60.4% sensitivity (95% CI: 45.3%-73.9%) and 83.2% specificity (95% CI: 74.1%-89.6%) in the training cohort. The performance of this two-gene panel showed no significant difference between different age and gender groups. When the two-gene panel was combined with CEA, the sensitivity for EC detection was further improved to 71.1%. In the validation cohort, the sensitivity of the two-gene panel for detecting EC, GC, and CRC was 60.0%, 30.0%, and 30.0%, respectively, with a specificity of 90.0%. Conclusion: The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers., Competing Interests: Authors GZ, YW, XW, and SX were employed by Suzhou VersaBio Technologies 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 © 2023 Pei, Zhao, Geng, Wang, Wang, Wang, Xiong and Zheng.)

Indacenodithiophene-benzothiadiazole (IDT-BT) has emerged as one of the most promising candidates for stretchable electronics due to its good stretchability and high mobility. Here, we present an air/liquid interface self-assembly method for the stretchable IDT-BT films and design an air-side transfer adherence strategy for improving the carrier mobility of IDT-BT. By controlling the cosolvent ratio in solution and the solvent evaporation rate, the large-scale intrinsically stretchable IDT-BT film with the diameter as high as ∼3 cm was self-assembled at the air/liquid interface. The resulting stretchable film with lightweight and good uniformity could be easily transferred to curved objects such as flexible 3 M tape, glass ball, and seashell. It is found that the transfer adherence strategy of the semiconductor film significantly affects the carrier transport. The transfer adherence from air-side can effectively decrease the number of the adsorbed water molecules at semiconductor/dielectric interface, which presents the mobility as high as 2.98 cm 2 V -1 s -1 . Based on the air/liquid interface self-assembled IDT-BT film, the peeling process of the film for preparation of full stretchable transistors could be eliminated. The resulting intrinsically stretchable transistor exhibits mobility higher than that of the transistor with a conventional spin-coated film. Our research provides new pathways for preparing the stretchable films and intrinsically stretchable organic field-effect transistors and shows the promising potential of the air/liquid interface self-assembly strategy for stretchable electronics.

Intrinsically stretchable gas sensors possess outstanding advantages in seamless conformability and high-comfort wearability for real-time detection toward skin/respiration gases, making them promising candidates for health monitoring and non-invasive disease diagnosis and therapy. However, the strain-induced deformation of the sensitive semiconductor layers possibly causes the sensing signal drift, resulting in failure in achievement of the reliable gas detection. Herein, a surprising result that the stretchable organic polymers present a universal strain-insensitive gas sensing property is shown. All the stretchable polymers with different degrees of crystallinity, including indacenodithiophene-benzothiadiazole (PIDTBT), diketo-pyrrolo-pyrrole bithiophene thienothiophene (DPPT-TT) and poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiad-iazolo [3,4-c] pyridine] (PCDTPT), show almost unchanged gas response signals in the different stretching states. This outstanding advantage enables the intrinsically stretchable devices to imperceptibly adhere on human skin and well conform to the versatile deformations such as bending, twisting, and stretching, with the highly strain-stable gas sensing property. The intrinsically stretchable PIDTBT sensor also demonstrates the excellent selectivity toward the skin-emitted trimethylamine (TMA) gas, with a theoretical limit of detection as low as 0.3 ppb. The work provides new insights into the preparation of the reliable skin-like gas sensors and highlights the potential applications in the real-time detection of skin gas and respiration gas for non-invasive medical treatment and disease diagnosis., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study aimed to explore the effects of Lactobacillus rhamnosus GG (LGG) supplementation on the growth performance, immune function, and antioxidant capacity of foals. Fifteen newborn foals with similar birth weight (51.67 ± 6.07 kg) and good health were randomly assigned to three groups: control group and test groups I and II, which were supplemented with 5.0 × 10 9 CFU/day and 1.0 × 10 10 CFU/day LGG, respectively, for 150 days. LGG intake increased the daily body height (P < .01) and weight (P < .01) gain of foals aged 120 to 150 days. The foals' IgA (P < .05) and IgG (P < .01) plasma levels increased at 30 and 150 days, respectively, and IL-6 plasma level increased at 90 days (P < .01). Plasma total antioxidant capacity level was significantly higher in test group I than in the control and test group II at 30 days (P < .01), whereas glutathione peroxidase level was significantly higher in test group II than in the control and test group I at 30 days (P < .01). Both test groups had significantly higher superoxide dismutase level than the control group (P < .01) and significantly decreased malondialdehyde plasma level at 90 and 150 days (P < .05). Overall, our findings indicate that dietary supplementation of LGG can improve the growth performance, immune function, and antioxidant capacity of newborn foals., Competing Interests: Declaration of Competing Interest None of authors have any conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Naoluoxintong (NLXT) has been used to treat ischemic stroke (IS) in China for more than two hundred years. However, the pharmacodynamic material basis of NLXT has not been fully studied. Under the guidance of the former network pharmacological analysis, a rapid and reliable method combining UPLC-Q-TOF-MS E with the novel informatics UNIFI™ platform was established which was used to study the composition of NLXT and its prototype components and metabolites in vivo . A total of 102 compounds were identified. 13 compounds were sourced from "Monarch herb", mainly involving flavonoids and their glycosides. 54 compounds were sourced from "Minister herb", mainly involving triterpenoid saponins, organic acids and lactones. 11 compounds were from the "Assistant herb", mostly containing citric acid and esters of citric acid. 24 compounds were from the "Guide herb", mostly including flavonoids and their glycosides, organic acids and lactones. Moreover, 24 prototype components and 30 metabolites were detected, and in vivo transformation pathways for different types of chemical components were provided. This is a comprehensive report on the identification of major chemical components in NLXT and metabolic components in rats by UPLC-Q-TOF-MS combined with UNIFI platform under the guidance of network pharmacology, which is helpful for the quality control of NLXT and the study of quality markers., Competing Interests: 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, (© 2023 Published by Elsevier Ltd.)

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

Grazing is a common approach to rearing. We investigated the effects of supplementation during grazing on milk yield and composition, blood biochemistry, and fecal microflora in Yili horses. The control mares grazed normally, while those in groups I and II received 1 kg/d of concentrate and 1 kg/d of concentrate + 0.4 kg/d of coated FA, respectively. Milk volumes were significantly higher in groups I and II than in the control group, and among the previous two, milk volumes were significantly higher in group II than in group I. Milk fat, lactose, and protein levels were significantly higher in group II than in the others. BUN was highly significantly lower in group I than in the control group. Specific FAs, total SFA, and total UFA were significantly higher in group II than in the other groups. After feeding, plasma GLU, free FA, TG, LDL, and VLDL were significantly higher in group II than in the other groups. The control group, group I, and group II had 4984, 5487, and 5158 OTUs, respectively, and 3483 OTUs were common to all groups. The abundance of Bacteroidetes and Firmicutes was >75%. The abundance of Verrucomicrobia was significantly higher in groups I and II than in the control group and, among the previous two, significantly higher in group II than in group I. The abundance of Treponema&#95;saccharophilum significantly differed between the control and other groups, and WCHB 1&#95;41 , Kiritimatiellae, and Verrucomicrobia abundances significantly differed between groups II and the other groups.

Colon cancer is a highly invasive and metastatic cancer with a poor prognosis. The University of Alabama at Birmingham Cancer data analysis portal (UALCAN) database indicates that potassium voltage-gated channel subfamily E member 4 (KCNE4) is highly expressed in colon cancer tissues. UALCAN data also show that KCNE4 expression is positively associated with individual cancer stages and negatively associated with patient survival. Therefore, the aim of the current study was to elucidate the functional role of KCNE4 in the biological behaviors of colon cancer cells and to investigate the underlying molecular mechanism. The gene EGF containing fibulin extracellular matrix protein 2 (EFEMP2) was found to be positively correlated with KCNE4 in colon cancer based on analysis performed using the LinkedOmics database; notably, upregulated EFEMP2 expression has been reported to be closely associated with the malignant phenotypes of colon cancer cells. The differences in the expression levels of KCNE4 and EFEMP2 between human colon cancer and normal colonic mucosa cell lines were assessed via reverse transcription-quantitative PCR and western blot assays. In addition, the proliferation, migration and invasion of colon cancer cells were determined using Cell Counting kit-8, colony formation, would healing and Transwell assays, and a co-immunoprecipitation assay was performed to confirm the interaction between KCNE4 and EFEMP2. The results of the study demonstrated that KCNE4 and EFEMP2 are markedly upregulated in colon cancer cells. In addition, KCNE4 interacted with and bound to EFEMP2. The suppressive effects of KCNE4 knockdown on the proliferation, colony formation, migration and invasion of colon cancer cells were attenuated by EFEMP2 overexpression. On the basis of these findings, it may be concluded that KCNE4 acts as an oncogene in colon cancer via the promotion of EFEMP2 expression., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Xu et al.)

Protective fabrics containing Zr-Based Metal-Organic Frameworks (Zr-MOFs) show great potential in the detoxification of chemical warfare agents (CWAs). However, the current studies still face the challenges of complicated fabrication processes, limited MOF loading mass, and insufficient protection. Herein, we developed a lightweight, flexible and mechanical robust aerogel by in situ growth of UiO-66-NH 2 onto aramid nanofibers (ANFs) and assembly of UiO-66-NH 2 loaded ANFs (UiO-66-NH 2 @ANFs) into 3D hierarchically porous architecture. The UiO-66-NH 2 @ANF aerogels feature high MOF loading of 261 %, high surface area of 589.349 m 2 g -1 , open and interconnected cellular structure, which provide efficient transfer channels and promote catalytic degradation of CWAs. As a result, the UiO-66-NH 2 @ANF aerogels demonstrate high 2-chloroethyl ethyl thioether (CEES) removal rate at 98.9 % and a short half-life of 8.15 min. Moreover, the aerogels present good mechanical stability (recovery rate of 93.3 % after 100 cycles under 30 % strain), low thermal conductivity (λ of 25.66 mW m -1 K -1 ), high flame resistance (LOI of 32 %) and good wearing comfortableness, indicating promising potential in multifunctional protection against CWAs., 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 Inc. All rights reserved.)

Recently, the theory of semi-tensor product (STP) method of matrices has received much attention from variety communities covering engineering, economics and industries, etc. This paper describes a detailed survey on some recent applications of the STP method in finite systems. First, some useful mathematical tools on the STP method are provided. Second, many recent developments about robustness analysis on the given finite systems are delineated, such as robust stable analysis of switched logical networks with time-delayed, robust set stabilization of Boolean control networks, event-triggered controller design for robust set stabilization of logical networks, stability analysis in distribution of probabilistic Boolean networks, and how to solve a disturbance decoupling problem by event triggered control for logical control networks. Finally, several research problems in future works are predicted.

The spoilage and forgery of perishable products such as food, drugs, and vaccines cause serious health hazards and economic loss every year. Developing highly efficient and convenient time-temperature indicators (TTIs) to realize quality monitoring and anticounterfeiting simultaneously is urgent but remains a challenge. To this end, a kind of colorimetric fluorescent TTI, based on CsPbBr 3 @SiO 2 nanoparticles with tunable quenching kinetics, is developed. The kinetics rate of the CsPbBr 3 -based TTIs is easily regulated by adjusting temperature, concentration of the nanoparticles, and addition of salts, stemming from the cation exchange effect, common-ion effect, and structural damage by water. Typically, when combined with europium complexes, the developed TTIs show an irreversible dynamic change in fluorescent colors from green to red upon increasing temperature and time. Furthermore, a locking encryption system with multiple logics is also realized by combining TTIs with different kinetics. The correct information only appears at specific ranges of time and temperature under UV light and is irreversibly self-erased afterward. The simple and low-cost composition and the ingenious design of kinetics-tunable fluorescence in this work stimulate more insights and inspiration toward intelligent TTIs, especially for high-security anticounterfeiting and quality monitoring, which is really conducive to ensuring food and medicine safety.

Background: Stool DNA test has been emerged as an effective noninvasive method for colorectal cancer (CRC) screening, but the real-world performance of stool DNA test in Chinese population has rarely been reported., Methods: A total of 36,527 subjects were recruited in Haining City from January 2021 to December 2021. Participants underwent primary screening by taking both two-samples fecal immunochemical tests (FITs) and high-risk factor questionnaire (HRFQ), and those who tested either positive by FITs or evaluated to be high risk by HRFQ were recommended to undertake subsequent stool DNA test and colonoscopy., Results: Of 36,527 participants, 34,778 (95%) completed both HRFQ and FITs, 9947 (29%) showed positive results during primary screening, and the colonoscopy compliance rate was 49%. Of primary screening positives, 8733 (88%) completed stool sample collections, and colonoscopy results from 4293 eligible participants were used for analyzing the performance of stool DNA test. The sensitivities for detecting CRC and advanced adenomas (AA) were 100% (95% CI: 60-100%) and 40% (95% CI: 34-46%), and the area under curve (AUC) was 0.961 (95% CI:0.954-0.967) and 0.625 (95% CI: 0.609-0.641), respectively. The specificity of stool DNA test was 84% (95% CI: 82-85%). The false-positive rate for stool DNA test is about 10% less than that of primary screening., Conclusion: Stool DNA test is a cost-effective and promising alternative strategy for CRC screening in China., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: This study aimed to perform a multicenter comparison between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD)., Background: Previous comparisons of RPD versus OPD have only been carried out in small, single-center studies of variable quality., Methods: Consecutive patients who underwent RPD (n = 1032) or OPD (n = 1154) at 7 centers in China between July 2012 and July 2020 were included. A 1:1 propensity score matching (PSM) was performed., Results: After PSM, 982 patients in each group were enrolled. The RPD group had significantly lower estimated blood loss (EBL) (190.0 vs 260.0 mL; P < 0.001), and a shorter postoperative 1length of hospital stay (LOS) (12.0 (9.0-16.0) days vs 14.5 (11.0-19.0) days; P < 0.001) than the OPD group. There were no significant differences in operative time, major morbidity including clinically relevant postoperative pancreatic fistula (CR-POPF), bile leakage, delayed gastric emptying, postoperative pancreatectomy hemorrhage (PPH), reoperation, readmission or 90-day mortality rates. Multivariable analysis showed R0 resection, CR-POPF, PPH and reoperation to be independent risk factors for 90-day mortality. Subgroup analysis on patients with pancreatic ductal adenocarcinoma (PDAC) (n = 326 in each subgroup) showed RPD had advantages over OPD in EBL and postoperative LOS. There were no significant differences in median disease-free survival (15.2 vs 14.3 months, P = 0.94) or median overall survival (24.2 vs 24.1 months, P = 0.88) between the 2 subgroups., Conclusions: RPD was comparable to OPD in feasibility and safety. For patients with PDAC, RPD resulted in similar oncologic and survival outcomes as OPD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study examined the effects of L-Cit supplementation on ram semen quality through metabolomics and transcriptomics. A total of 16 rams were randomly categorized into two groups. The control group was fed a basic diet, whereas the experimental group received feed supplemented with 12 g/d of L-Cit. Semen and blood were collected from the rams on days 0 and 72 to measure sugar, pyruvate, amino acid, and nontargeted metabolite contents. Additionally, hypothalamic and testicular tissues were collected for a transcriptomic analysis. We found 27 differential metabolites between the control and experimental groups, of which 21 were downregulated (p < 0.05) and 6 were upregulated (p < 0.05). Compared with the control group, xylose and pyruvate contents in seminal plasma increased by 43.86% and 162.71%, respectively (p < 0.01). Additionally, the levels of 11 amino acids showed a significant increase in seminal plasma (p < 0.01). Furthermore, 961 and 715 differentially expressed genes were detected in the hypothalamic and testicular tissues, respectively. The pathways of significant enrichment in the hypothalamus and testes were protein digestion, absorption, glycolysis/gluconeogenesis, and amino as well as nucleotide sugar metabolisms. In the present study, L-Cit improved protein synthesis and blood metabolism, consequently increasing the contents of most amino acids in ram seminal plasma. Specifically, the hypothalamus controlled the expression of glycolysis/gluconeogenesis-related genes in the testes through its metabolites released into the serum, thereby providing energy for sperm production, which led to a decrease in the sugar content of seminal plasma.

Purpose: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest., Materials and Methods: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed., Results: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up., Conclusions: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Ethnopharmacological Relevance: The classic traditional Chinese compound Naoluoxintong (NLXT) has been proven an effective remedy for ischemic stroke (IS). The protective effect of NLXT on neural stem cells (NSCs), however, remains unclear., Aim of the Study: To investigate the protective effect of NLXT on NSCs in rats with middle cerebral artery occlusion (MCAO) and the effect of Nestin expression in vivo., Materials and Methods: Sprague-Dawley (SD) rats were randomly divided into three groups: the sham-operated group, the MCAO model group and the NLXT group. The MCAO model in rats was established by modified Longa wire embolization method. The sham-operated group, the model group and the NLXT groups were divided into three subgroups according to the sampling time points of 1 d, 3 d and 7 d after successful model-making. Immunofluorescence staining, including bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP), β-tubulinIII/GFAP, BrdU/doublecortin (DCX) and BrdU/neuronal nuclei (NeuN), was used to detect the proliferation and survival of NSCs in the hippocampal after drug administration. Protein expression of Nestin, DCX, GFAP and NeuN in the hippocampal was detected by Western blot (WB)., Results: Immunofluorescence experiment of Nestin labeled: on the first day, a few Nestin-positive cells were found in the hippocampal DG area. Afterwards, the number of Nestin-labeled positive cells in the model group increased, while the number of cells in the sham group did not fluctuate significantly. The number of positive cells in each administration group increased more than that in the model and normal group. β-tubulin III/GFAP double-labeled: a small amount of double labeled cells was expressed in the normal group, and the number subsequently fluctuated little. In the model group, β-tubulin III/GFAP positive cells increased initially after acute ischemia, and gradually decreased afterwards. In the NLXT-treated group, β-Tubulin III positive cells were significantly increased on day 1, 3 and 7, while GFAP positive cells had little change. BrdU/DCX double-labeled: initially, a small number of BrdU/DCX-labeled positive cells were observed in the normal group and the model group, but there was no increasing trend over time. The positive cells in the NLXT group increased over time, and those in the seven-day group were significantly higher than those in the one-day and three-day groups. BrdU/NEUN double-labeled: in the normal group, BrdU/NEUN positive cells were enriched and distributed regularly. The number of positive cells in the model group was small and decreased gradually with time, and the decrease was most obvious on the third day. The number of positive cells in the NLXT group was significantly higher than that in the model group, and the number of positive cells in the seven-day group was significantly higher than that in the one-day and three-day groups. WB results reflected those three proteins, Nestin, NeuN and DCX, showed an increase in expression, except GFAP, which showed a decreasing trend., Conclusions: Preliminarily, NLXT can promote the migration and differentiation of NSCs. It may have a protective effect on the brain by promoting repair of brain tissue damage through upregulation of Nestin after IS., 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.)

Introduction: Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance., Methods: We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set., Result: Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve [AUC] = 100.00%). AC005786.3 (Mean [|SHAP value|] = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE-A3 immunotherapy against metastatic melanoma (AUC = 100.00%)., Discussion: This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment., 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 © 2022 Jin, Yang, Chi, Wei, Zhang, Zhao, Chen, Xia and Li.)

Background: Sorafenib is a multi-kinase inhibitor that shows antitumor activity in advanced hepatocellular carcinoma. Sorafenib exerts a regulatory effect on immune cells, including T cells, natural killer cells and dendritic cells. Studies have shown that plasmacytoid dendritic cells (pDCs) are functionally impaired in cancer tissues or produce low type I interferon alpha (IFNα) in cancer microenvironments. However, the effects of sorafenib on the function of pDCs have not been evaluated in detail., Methods: Normal and patient PBMCs were stimulated with CpG-A to evaluate IFNα production with Flow cytometry and ELISA., Result: We analyzed the production of IFNα by PBMCs in patients with advanced HCC under sorafenib treatment. We found that sorafenib-treated HCC patients produced less IFNα than untreated patients. Furthermore, we demonstrated that sorafenib suppressed the production of IFNα by PBMCs or pDCs from heathy donors in a concentration-dependent manner., Conclusion: Sorafenib suppressed pDCs function. Given that sorafenib is a currently recommended targeted therapeutic agent against cancer, our results suggest that its immunosuppressive effect on pDCs should be considered during treatment., (© 2022. The Author(s).)

Rationale: Penetrating brain injury (PBI) is a rare trauma that presents as a difficult and serious surgical emergency for neurosurgeons in clinical practice. Our patient was admitted with a PBI caused by a tire explosion, which is an extremely rare cause of injury., Patient Concerns: We report a case of a 28-year-old male patient who suffered a PBI when a tire exploded while it was being inflated with a high-pressure air pump., Diagnoses: The patient was diagnosed with PBI presenting with multiple comminuted skull fractures, massive bone fragments with foreign bodies penetrating the underlying brain tissue of the top right frontal bone, multiple cerebral contusions, and intracranial hematoma., Interventions: Emergency combined multidisciplinary surgery was performed for the removal of the fragmented bone pieces, hematoma, and foreign bodies; decompression of the debridement flap; reconstruction of the anterior skull base; and repair of the dura mater., Outcomes: The patient was successfully resuscitated and discharged 1 month later and is now recovering well., Lessons: Patients with PBI are critically ill. Therefore, timely, targeted examinations and appropriate multidisciplinary interventions through a green channel play a key role in assessing the condition, developing protocols, and preventing complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods for the early detection of UGC., Methods: A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers ( ELMO1 , ZNF582 and TFPI2 ) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects., Results: The results indicated excellent PCR amplification efficiency and reproducibility of ELMO1 , ZNF582 and TFPI2 in the range of 10-100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of ELMO1 , ZNF582 and TFPI2 were significantly higher in UGC samples than those in control subjects. The sensitivities of ELMO1 , ZNF582 and TFPI2 alone for UGC detection were 32.3%, 61.3% and 30.6%, respectively; when three markers were combined, the sensitivity was improved to 71.0%, with a specificity of 90.0%, and the area under the curve (AUC) was 0.870 (95% CI: 0.832-0.902)., Conclusion: Methylated ELMO1 , ZNF582 and TFPI2 were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.

Background: ColoDefense1.0 assay has demonstrated its excellent sensitivity and specificity for early detection of colorectal cancer (CRC) by detecting the methylation levels of SDC2 and SEPT9, while exhibited limitations on relatively large sample capacity required and limited detection throughput by applying triplicate PCR reactions for each sample. In this study, ColoDefense1.0 was simplified and optimized into ColoDefense2.0 in a single PCR reaction., Methods: A total 529 stool specimens were collected, and 244 CRC patients, 34 patients with advanced adenomas (AA), 64 with small polyps (SP) and 187 control subjects were divided in training and validation cohorts. Methylation levels of SEPT9 and SDC2 were examined by qPCR reactions in triplicate or single., Results: The stool DNA quantity stored in preservative buffer at 37 °C up to 7 days exhibited no significant decrease. In the training cohort, when the number of replicates reduced from 3 to 1, the overall performance of ColoDefense2.0 was identical to that of ColoDefense1.0, showing sensitivities of 71.4% for AA and 90.8% for all stage CRC with a specificity of 92.9%. In the validation cohort, sensitivities of SP, AA and CRC using ColoDefense2.0 were 25.0%, 55.0% and 88.2%, increased from 14.1% (20.3%), 40.0% (40.0%) and 79.4% (67.6%) using SDC2 (SEPT9) alone; along with an overall specificity of 90.2%, decreased from 94.1% (95.1%) using SDC2 (SEPT9) alone., Conclusion: The simplified ColoDefense test maintained the overall performance while reduced the number of PCR reactions to 1/3, and provided an effective and convenient tool to detect early CRC and precancerous lesions and potentially improve the compliance of screening., (© 2022. The Author(s).)

Background: Gastric cancer (GC) is a leading cause of cancer death and an important barrier to increasing life expectancy in China. Early detection of GC can significantly reduce its mortality rate., Methods: A new plasma-based multiplex DNA methylation assay combining simultaneous detection of three biomarkers (KCNQ5, C9orf50 and CLIP4) and one control gene (ACTB) was developed. It was used to examine 12 paired tissue samples and a training cohort of 151 plasma samples. Its performance was subsequently confirmed in validation cohort 1 (n = 105) and validation cohort 2 (n = 139)., Results: Three methylation markers showed significantly higher methylation levels in GC tissues than in paired adjacent tissues. The assay showed a sensitivity of 67.9 % with a specificity of 86.6 % for GC detection in the training cohort, and the AUC was 0.786 (95 % CI: 0.701-0.855). The methylation levels in GC patients were significantly higher than those in benign gastric tumors and in control group. Meanwhile, the assay achieved a sensitivity of 65.5 % with a specificity of 90.0 % in the validation cohort 1, and the AUC was 0.805 (95 % CI: 0.716-0.876). In the validation cohort 2, its sensitivity and specificity were 73.7 % and 84.1 %, respectively, and the AUC was 0.851 (95 % CI: 0.776-0.909)., Conclusion: The plasma-based multiplex DNA methylation assay was highly specific for GC early detection. It has the potential to become an alternative approach to improve diagnosis of GC in the clinics., Competing Interests: Declaration of Competing Interest Authors Guodong Zhao, Kai Wang, Weifeng Wang and Shangmin Xiong are employed by Suzhou VersaBio Technologies 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 Elsevier GmbH. All rights reserved.)