Beyond graft function impairment after liver transplantation: the prolonged cold ischemia time impact on recurrence of hepatocellular carcinoma after liver transplantation-a single-center retrospective study.

Purpose: Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. Patients and Methods: This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. Results: A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p = 0.012), and the incidence of early allograft dysfunction (EAD) (p = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045). Conclusion: An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.

Frontal and parietal cortices activation during walking is repeatable in older adults based on fNIRS.

Purpose: This study aimed to explore the test-retest reliability of fNIRS in measuring frontal and parietal cortices activation during straight walking and turning walking in older adults, in order to provide a theoretical foundation for selecting assessment tools for clinical research on motor control and some diseases such as Parkinson's disease in older adults. Methods: 18 healthy older participants (69.1 ± 0.7 years) were included in this study. The participants completed straight walking and figure-of-eight turning walking tasks at self-selected speeds. Intra-class correlation coefficients (ICCs) and Bland-Altman scatter plots were used to assess the test-retest reliability of oxyhemoglobin (HbO2) changes derived from fNIRS. p < 0.05 was considered statistically significant. Results: The test-retest reliability of HbO2 in prefrontal cortex (ICC, 0.67-0.78) was good and excellent, in frontal motor cortex (ICC, 0.51-0.61) and parietal sensory cortex (ICC, 0.53-0.62) is fair and good when the older adults performed straight and turning walking tasks. Bland-Altman diagram shows that the data consistency is fair and good. Conclusion: fNIRS can be used as a clinical measurement method to evaluate the brain activation of the older adults when walking in a straight line and turning, and the results are acceptable repeatability and consistency. However, it is necessary to strictly control the testing process and consider the possible changes in the repeated measurements.

Rapid and highly sensitive colorimetric LAMP assay and integrated device for visual detection of monkeypox virus.

BACKGROUND: The monkeypox virus (MPXV) is a linear double-stranded DNA virus with a large genome that causes tens of thousands of infections and hundreds of deaths in at least 40 countries and regions worldwide. Therefore, timely and accurate diagnostic testing could be an important measure to prevent the ongoing spread of MPXV and widespread epidemics. RESULTS: Here, we designed multiple sets of primers for the target region of MPXV for loop-mediated isothermal amplification (LAMP) detection and identified the optimal primer set. Then, the specificity in fluorescent LAMP detection was verified using the plasmids containing the target gene, pseudovirus and other DNA/RNA viruses. We also evaluated the sensitivity of the colorimetric LAMP detection system using the plasmid and pseudovirus samples, respectively. Besides, we used monkeypox pseudovirus to simulate real samples for detection. Subsequent to the establishment and introduction of a magnetic beads (MBs)-based nucleic acid extraction technique, an integrated device was developed, characterized by rapidity, high sensitivity, and remarkable specificity. This portable system demonstrated a visual detection limit of 137 copies/mL, achieving sample-to-answer detection within 1 h. SIGNIFICANCE: The device has the advantages of integration, simplicity, miniaturization, and visualization, which help promote the realization of accurate, rapid, portable, and low-cost testing. Meanwhile, this platform could facilitate efficient, cost-effective and easy-operable point-of-care testing (POCT) in diverse resource-limited settings in addition to the laboratory.

Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts.

BACKGROUND/AIMS: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. METHODS: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. RESULTS: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). CONCLUSION: FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Transport Properties with Multiple Functions of Fe@C60-GNR Single Molecule.

Encouraged by the successful fabrication of C60-GNR (GNR=graphene nanoribbon) single-molecule transistors in experiments, four Fe-containing derived double-layered devices of Fe@C60-GNR are designed by employing different electrode linkages and their transport properties are investigated by using density functional theory (DFT) and nonequilibrium Green's function (NEGF) methods. Regardless of electrode connection, all these devices give rise to a smaller negative differential resistance (NDR) peak at V=0.2 and a higher peak at 1.2 V, suggesting their stable maneuverability as molecular devices and good candidates for developing on(off)-off(on)-on(off) current switches. The macroscopic NDR performance depends on the delocalization character and the crossing mechanism of the frontier orbitals. The peak-to-valley current ratios (Rmax) range from 454 to 2737, determined by the electrode linkage. Such a large Rmax-value is necessary for developing dynamic random-access memory (DRAM) cells. Encapsulating the Fe atom inside C60 not only improves the conductivity but also introduces the spin-polarized transport property. The spin-filtering efficiency (SFE) of almost all devices oscillates up and down in response to the bias voltage, indicating the possibility of designing on(off)-off(on)-on(off) spin switches and up-down spin switches. All these fascinating properties provide an important clue for designing similar molecular devices with multiple functions by trapping magnetic transition metal atoms inside fullerenes.

Factors influencing functional outcome of fractures of the anterior process of the calcaneus.

INTRODUCTION: Fractures of the anterior process of the calcaneus (APC) are easily overlooked in clinical practice. Most patients have good to excellent clinical outcome after conservative treatment, while some patients may have persisting symptoms and unfavorable functional outcomes. The aim of this study was to identify the risk factors associated with unfavorable functional outcome after conservative treatment in APC fractures. METHODS: All patients presenting with APC fractures and receiving conservative treatment from April 2019 to April 2020 were retrospectively assessed. The primary outcome measurement was the ankle joint function assessed using Karlsson Scoring System at 2 years post-injury. The risk factors associated with unfavorable functional outcomes (Karlsson score ≤ 80) were evaluated by logistic regression analysis. RESULTS: In total, 84 patients were included with a mean age of 40 years. 26 (31%) patients presented with unfavorable functional outcome at 2 years post-injury. In multivariate logistic regression, concomitant fractures of talonavicular (TN) joints and older age were significantly associated with unfavorable functional outcome (p<0.05). Patients with concomitant fractures of TN joints had an odds ratio of 3.623 for unfavorable functional outcome. The optimal cutoff age for an unfavorable outcome was ≥ 47.5 years, with an odds ratio of 5.010. CONCLUSION: Most patients with APC fractures achieved good to excellent results when treated conservatively. Attention should be paid to those with concomitant fractures of TN joints and with age ≥ 47.5 years, which might lead to unfavorable functional recovery. LEVEL OF EVIDENCE: IV; case series.

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice.

Background: T cell-mediated acute rejection(AR) after heart transplantation(HT) ultimately results in graft failure and is a common indication for secondary transplantation. It's a serious threat to heart transplant recipients. This study aimed to explore the novel lncRNA-miRNA-mRNA networks that contributed to AR in a mouse heart transplantation model. Methods: The donor heart from Babl/C mice was transplanted to C57BL/6 mice with heterotopic implantation to the abdominal cavity. The control group was syngeneic heart transplantation with the same kind of mice donor. The whole-transcriptome sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in mouse heart allograft. The biological functions of ceRNA networks was analyzed by GO and KEGG enrichment. Differentially expressed ceRNA involved in programmed cell death were further verified with qRT-PCR testing. Results: Lots of DEmRNAs, DEmiRNAs and DElncRNAs were identified in acute rejection and control after heart transplantation, including up-regulated 4754 DEmRNAs, 1634 DElncRNAs, 182 DEmiRNAs, and down-regulated 4365 DEmRNAs, 1761 DElncRNAs, 132 DEmiRNAs. Based on the ceRNA theory, lncRNA-miRNA-mRNA regulatory networks were constructed in allograft acute rejection response. The functional enrichment analysis indicate that the down-regulated mRNAs are mainly involved in cardiac muscle cell contraction, potassium channel activity, etc. and the up-regulated mRNAs are mainly involved in T cell differentiation and mononuclear cell migration, etc. The KEGG pathway enrichment analysis showed that the down-regulated DEmRNAs were mainly enriched in adrenergic signaling, axon guidance, calcium signaling pathway, etc. The up-regulated DEmRNAs were enriched in the adhesion function, chemokine signaling pathway, apoptosis, etc. Four lncRNA-mediated ceRNA regulatory pathways, Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox, 1700071M16Rik/miR-145a-3p/Themis2, were finally validated. In addition, increased expression of PVT1, 1700071M16Rik, Tox and Themis2 may be considered as potential diagnostic gene biomarkers in AR. Conclusion: We speculated that Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox and 1700071M16Rik/miR-145a-3p/Themis2 interaction pairs may serve as potential biomarkers in AR after HT.

Characterization, complete genome sequencing, and CRISPR/Cas9 system-based decontamination of a novel Escherichia coli phage TR1 from fermentation substrates.

Phage contamination has become a major concern for industrial bacteria, such as Escherichia coli BL21(DE3), used in fermentation processes. Herein, we report a CRISPR/Cas9 defense system-based strategy to precisely prey and degrade phage DNA to decontaminate target phages. First, we isolated a novel phage from fermentation substrates with BL21(DE3) as the host, named TR1. It showed a typical podovirus morphology with a head diameter of 51.46 ± 2.04 nm and a tail length of 9.31 ± 2.77 nm. The burst size of phage TR1 was 151 PFU/cell, suggesting its strong fecundity in the fermentation system. Additionally, whole-genome sequencing revealed that phage TR1 has a DNA genome of 44,099 bp in length with a 43.8% GC content, encoding a total of 68 open reading frames. Comparative genomics and phylogenetic analysis designated this phage to be a new species of the genus Christensenvirus. To counteract phage TR1, we employed the CRISPR/Cas9 system-based strategy and constructed two phage-resistant E. coli strains, BL21-C and BL21-T, based on conserved genes. Both EOP assays and growth curves indicated strong phage resistance of the recombinant strains, without affecting cell growth. Therefore, this study aimed to provide a resilient strategy to respond to ever-changing phages and ongoing phage-host arm race in industrial fermentation environments by the personalized design of spacers in the recombinant CRISPR/Cas system-containing plasmid. More importantly, our research sparks the use of phage defense mechanism to prevent phage contamination in extensive biotechnological applications.

Utilization of hepatitis B surface antigen-positive donors in liver transplantation for recipients with hepatocellular carcinoma: a retrospective and propensity score matching analysis.

Introduction: The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Methods: Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. Results: PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P > 0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P = 0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P = 0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P = 0.005 and 0.025, respectively). Conclusion: In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.

A meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production.

Actinobacteria are ubiquitous bacteria undergoing complex developmental transitions coinciding with antibiotic production in response to stress or nutrient starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate these intriguing cell biological processes remain unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA and disrupted the signal transduction of c-di-GMP, thus governing both developmental transition and antibiotic production. Additionally, practical mutation of BldDK11R bypassing acetylation regulation could enhance the positive effect of BldD on antibiotic production. The study of AcP-dependent acetylation is usually confined to the control of enzyme activity. Our finding represents an entirely different role of the covalent modification caused by AcP, which integrated with c-di-GMP signal in modulating the activity of BldD for development and antibiotic production, coping with environmental stress. This coherent regulatory network might be widespread across actinobacteria, thus has broad implications.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study.

BACKGROUND: The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures. MATERIALS AND METHODS: Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations. RESULTS: Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00-2.51; PMS<7: RR=1.49, 95% CI: 1.13-2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57-2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (-0.44 units 95% CI: -0.70 to -0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS. CONCLUSIONS: The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.

Relationship between motor performance and cortical activity of older neurological disorder patients with dyskinesia using fNIRS: A systematic review.

Background: Neurological disorders with dyskinesia would seriously affect older people's daily activities, which is not only associated with the degeneration or injury of the musculoskeletal or the nervous system but also associated with complex linkage between them. This study aims to review the relationship between motor performance and cortical activity of typical older neurological disorder patients with dyskinesia during walking and balance tasks. Methods: Scopus, PubMed, and Web of Science databases were searched. Articles that described gait or balance performance and cortical activity of older Parkinson's disease (PD), multiple sclerosis, and stroke patients using functional near-infrared spectroscopy were screened by the reviewers. A total of 23 full-text articles were included for review, following an initial yield of 377 studies. Results: Participants were mostly PD patients, the prefrontal cortex was the favorite region of interest, and walking was the most popular test motor task, interventional studies were four. Seven studies used statistical methods to interpret the relationship between motor performance and cortical activation. The motor performance and cortical activation were simultaneously affected under difficult walking and balance task conditions. The concurrent changes of motor performance and cortical activation in reviewed studies contained the same direction change and different direction change. Conclusion: Most of the reviewed studies reported poor motor performance and increased cortical activation of PD, stroke and multiple sclerosis older patients. The external motor performance such as step speed were analyzed only. The design and results were not comprehensive and profound. More than 5 weeks walking training or physiotherapy can contribute to motor function promotion as well as cortices activation of PD and stroke patients. Thus, further study is needed for more statistical analysis on the relationship between motor performance and activation of the motor-related cortex. More different type and program sports training intervention studies are needed to perform.

Effect of fermentation on structural properties and antioxidant activity of wheat gluten by Bacillus subtilis.

Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.

Fermented Wheat Germ Alleviates Depression-like Behavior in Rats with Chronic and Unpredictable Mild Stress.

Depression is a chronic mental illness with devastating effects on a person's physical and mental health. Studies have reported that food fermentation with probiotics can enrich the nutritional values of food and produce functional microorganisms that can alleviate depression and anxiety. Wheat germ is an inexpensive raw material that is rich in bioactive ingredients. For example, gamma-aminobutyric acid (GABA) is reported to have antidepressant effects. Several studies concluded that Lactobacillus plantarum is a GABA-producing bacteria and can alleviate depression. Herein, fermented wheat germs (FWGs) were used to treat stress-induced depression. FWG was prepared by fermenting wheat germs with Lactobacillus plantarum. The chronic unpredictable mild stress (CUMS) model was established in rats, and these rats were treated with FWG for four weeks to evaluate the effects of FWG in relieving depression. In addition, the study also analyzed the potential anti-depressive mechanism of FWG based on behavioral changes, physiological and biochemical index changes, and intestinal flora changes in depressed rats. The results demonstrated that FWG improved depression-like behaviors and increased neurotransmitter levels in the hippocampus of CUMS model rats. In addition, FWG effectively altered the gut microbiota structure and remodeled the gut microbiota in CUMS rats, restored neurotransmitter levels in depressed rats through the brain-gut axis, and restored amino acid metabolic functions. In conclusion, we suggest that FWG has antidepressant effects, and its potential mechanism may act by restoring the disordered brain-gut axis.

Identification of a tsRNA Contributor to Impaired Diabetic Wound Healing via High Glucose-Induced Endothelial Dysfunction.

Purpose: Delayed skin healing in diabetic wounds is a major clinical problem. The tRNA-derived small RNAs (tsRNAs) were reported to be associated with diabetes. However, the role of tsRNAs in diabetic wound healing is unclear. Our study was designed to explore the tsRNA expression profile and mine key potential tsRNAs and their mechanism in diabetic wounds. Methods: Skin tissues of patients with diabetic foot ulcers and healthy controls were subjected to small RNA sequencing. The role of candidate tsRNA was explored by loss- and gain-of-function experiments in HUVECs. Results: A total of 55 differentially expressed tsRNAs were identified, including 12 upregulated and 43 downregulated in the diabetes group compared with the control group. These tsRNAs were mainly concentrated in intercellular interactions and neural function regulation in GO terms and enriched in MAPK, insulin, FoxO, calcium, Ras, ErbB, Wnt, T cell receptor, and cGMP-PKG signaling pathways. tRF-Gly-CCC-039 expression was upregulated in vivo and in vitro in the diabetic model. High glucose disturbed endothelial function in HUVECs, and tRF-Gly-CCC-039 mimics further harmed HUVECs function, characterized by the suppression of proliferation, migration, tube formation, and the expression of Coll1a1, Coll4a2, and MMP9. Conversely, the tRF-Gly-CCC-039 inhibitor could attenuate high-glucose-induced endothelial injury to HUVECs. Conclusion: We investigated the tsRNAs expression profile in diabetic foot ulcers and defined the impairment role of tRF-Gly-CCC-039 in endothelial function in HUVECs. This study may provide novel insights into accelerating diabetic skin wound healing.

Mining and Characterization of Thermophilic Glucose Isomerase Based on Virtual Probe Technology.

Fructose, which is produced by the isomerization of glucose isomerase, is a crucial precursor for the biosynthesis of rare sugars. In this study, thermophilic glucose isomerases (GI) from Caldicellulosiruptor acetigenus (CAGI), Thermoanaerobacter thermocopriae (TTGI), and Thermotoga petrophila (TPGI) were screened from GenBank database by a virtual probe and were successfully expressed in Escherichia coli BL21(DE3). The results of characterization demonstrated that the optimal pH for CAGI and TTGI were 8.0 and were maintained at 80% in a slightly acidic environment. The relative residual activities of CAGI and TTGI were found to be 40.6% and 52.6%, respectively, following an incubation period of 24 h at 90 ℃. Furthermore, CAGI and TTGI exhibited superior catalytic performance that their reaction equilibrium both reached only after an hour at 85 ℃ with 200 g/L glucose, and the highest conversion rates were 54.2% and 54.1%, respectively. This study identifies competitive enzyme candidates for fructose production in the industry with appreciable cost reduction.

Construction and Enhanced Efficiency of Bi2MoO6/ZnO Compo-Sites for Visible-Light-Driven Photocatalytic Performance.

Bi2MoO6 was one of the important bismuth-based semiconductors with a narrow bandgap, and has been widely used in selective oxidation catalysts, supercapacitors, and energy-storage devices. A series of Bi2MoO6/ZnO composite photocatalysts with different mass ratios were synthesized by the hydrothermal method. The synthesized samples were characterized by XRD, PL, UV-Vis, SEM, TEM, XPS, and BET analysis techniques. Under visible light conditions, Methylene blue (MB) was used as the target degradation product to evaluate its photocatalytic performance. The results showed that the degradation rate constant of Bi2MoO6/ZnO (0.4-BZO) was about twice that of the traditional photocatalysis of ZnO. The Bi2MoO6/ZnO composite catalyst maintained stable performance after four consecutive runs. The high photocatalytic activity of Bi2MoO6/ZnO was attributed to the efficient electron transport of the heterojunction, which accelerates the separation of electron-hole pairs and reduces the probability of carrier recombination near the Bi2MoO6/ZnO heterojunction. Bi2MoO6/ZnO nanocomposites have potential applications in the field of photodegradation.

Protein acylation links metabolism and the control of signal transduction, transcription regulation, growth, and pathogenicity in Actinobacteria.

Actinobacteria have a complex life cycle, including morphological and physiological differentiation which are often associated with the biosynthesis of secondary metabolites. Recently, increased interest in post-translational modifications (PTMs) in these Gram-positive bacteria has highlighted the importance of PTMs as signals that provide functional diversity and regulation by modifying proteins to respond to diverse stimuli. Here, we review the developments in research on acylation, a typical PTM that uses acyl-CoA or related metabolites as donors, as well as the understanding of the direct link provided by acylation between cell metabolism and signal transduction, transcriptional regulation, cell growth, and pathogenicity in Actinobacteria.