Infection and intracellular transport of white spot syndrome virus require the ESCRT machinery in shrimp.

The cellular endosomal sorting complex required for transport (ESCRT) system comprises five distinct components and is involved in many different physiological processes. Recent studies have shown that different viruses rely upon the host ESCRT system for viral infection. However, whether this system is involved in white spot syndrome virus (WSSV) infection remains unclear. Here, we identified 24 homologs of ESCRT subunits in kuruma shrimp, Marsupenaeus japonicus, and found that some key components were strongly upregulated in shrimp after WSSV infection. Knockdown of key components of the ESCRT system using RNA interference inhibited virus replication, suggesting that the ESCRT system is beneficial for WSSV infection. We further focused on TSG101, a crucial member of the ESCRT-I family that plays a central role in recognizing cargo and activating the ESCRT-II and ESCRT-III complexes. TSG101 colocalized with WSSV in hemocytes. The addition of N16 (a TSG101 inhibitor) markedly decreased WSSV replication. TSG101 and ALIX of the ESCRT system interact with WSSV envelope proteins. The host proteins TSG101, RAB5, and RAB7, the viral protein VP28, and DNA were detected in endosomes isolated from hemocytes of WSSV-infected shrimp. Knockdown of Rab5 and Rab7 expression reduced viral replication. Taken together, these results suggest that the ESCRT system is hijacked by WSSV for transport through the early to late endosome pathway. Our work identified a novel requirement for the intracellular trafficking and infection of WSSV, and provided novel therapeutic targets for the prevention and control of WSSV in shrimp aquaculture. IMPORTANCE: Viruses utilize the ESCRT machinery in a variety of strategies for their replication and infection. This study revealed that the interaction of ESCRT complexes with WSSV envelope proteins plays a crucial role in WSSV infection in shrimp. The ESCRT system is conserved in the shrimp Marsupenaeus japonicus, and 24 homologs of the ESCRT system were identified in the shrimp. WSSV exploits the ESCRT system for transport and propagation via the interaction of envelope proteins with host TSG101 and ALIX in an endosome pathway-dependent manner. Understanding the underlying mechanisms of WSSV infection is important for disease control and breeding in shrimp aquaculture.

Social experiences switch states of memory engrams through regulating hippocampal Rac1 activity.

In pathological or artificial conditions, memory can be formed as silenced engrams that are unavailable for retrieval by presenting conditioned stimuli but can be artificially switched into the latent state so that natural recall is allowed. However, it remains unclear whether such different states of engrams bear any physiological significance and can be switched through physiological mechanisms. Here, we show that an acute social reward experience switches the silent memory engram into the latent state. Conversely, an acute social stress causes transient forgetting via turning a latent memory engram into a silent state. Such emotion-driven bidirectional switching between latent and silent states of engrams is mediated through regulation of Rac1 activity­dependent reversible forgetting in the hippocampus, as stress-activated Rac1 suppresses retrieval, while reward recovers silenced memory under amnesia by inhibiting Rac1. Thus, data presented reveal hippocampal Rac1 activity as the basis for emotion-mediated switching between latent and silent engrams to achieve emotion-driven behavioral flexibility.

Activatable Dual-Optical Molecular Probe for Bioimaging Superoxide Anion in Epilepsy.

Superoxide anion (O2•-) plays a pivotal role in the generation of other reactive oxygen species within the body and is closely linked to epilepsy. Despite this connection, achieving precise imaging of O2•- during epilepsy pathology remains a formidable challenge. Herein, we develop an activatable molecular probe, CL-SA, to track the fluctuation of the level of O2•- in epilepsy through simultaneous fluorescence imaging and chemiluminescence sensing. The developed probe CL-SA demonstrated its efficacy in imaging of O2•- in neuronal cells, showcasing its dual optical imaging capability for O2•- in vitro. Furthermore, CL-SA was successfully used to observe aberrantly expressed O2•- in a mouse model of epilepsy. Overall, CL-SA provides us with a valuable tool for chemical and biomedical studies of O2•-, promoting the investigation of O2•- fluctuations in epilepsy, as well as providing a reliable means to explore the diagnosis and therapy of epilepsy.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum.

BACKGROUND: Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses. RESULTS: TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance. CONCLUSIONS: TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

Dark solitons and their bound states in a nonlinear fiber with second- and fourth-order dispersion.

We study the excitations of dark solitons in a nonlinear optical fiber with the second- and fourth-order dispersion, and find the emergence of striped dark solitons (SDSs) and some multi-dark-soliton bound states. The SDSs can exhibit time-domain oscillating structures on a plane wave, and they have two types: the ones with or without the total phase step, while the multi-dark-soliton bound states exhibit different numbers of amplitude humps. By the modified linear stability analysis, we regard the SDSs as the results of the competition between periodicity and localization, and analytically give their existence condition, oscillation frequency, and propagation stability, which show good agreements with numerical results. We also provide a possible interpretation of the formation of the existing striped bright solitons (SBSs), and find that SBS will become the pure-quartic soliton when its periodicity and localization carry equal weight. Our results provide the theoretical support for the experimental observation of striped solitons in nonlinear fibers, and our method can also guide the discovery of striped solitons in other physical systems.

Does rAj-Tspin, a novel peptide from A. japonicus, exert antihepatocellular carcinoma effects via the ITGB1/ZYX/FAK/AKT signaling pathway?

rAj-Tspin, a soluble recombinant peptide from Apostichopus japonicus, can inhibit the integrin ß1 (ITGB1)/FAK/AKT signaling pathway in hepatocellular carcinoma (HCC) via cell epithelial-mesenchymal transition (EMT) and apoptosis. Zyxin (ZYX) is a focal adhesion protein that is considered a novel mediator of EMT and apoptosis. However, the inhibitory mechanisms of rAj-Tspin in HCC and whether it is related to ZYX are unclear. We examined the antitumor effect of rAj-Tspin on the Huh7 human HCC cell line and on a nude mouse model generated via subcutaneous injection or orthotopic intrahepatic transplantation of Huh7 cells. Our results revealed that rAj-Tspin strikingly reduced the viability and promoted the apoptosis of Huh7 cells and inhibited HCC tumor growth in nude mice. rAj-Tspin inhibited ITGB1 and ZYX protein expression in vivo and in vitro in a dose-dependent manner. Mechanistically, the FAK/AKT signaling pathway and the proliferation and invasion of HCC cells were suppressed upon ITGB1 and ZYX knockdown. Moreover, the effect of ITGB1 overexpression on the growth of HCC cells was inhibited by rAj-Tspin. In contrast, the promoting effect of ITGB1 overexpression could be inhibited by ZYX knockdown. ZYX knockdown had no effect on ITGB1 expression. These findings suggest that ZYX is required for the indispensable role of ITGB1 in rAj-Tspin-alleviated HCC and provide an important therapeutic target for HCC. In summary, the anti-HCC effect of rAj-Tspin potentially involves the regulation of the ITGB1/ZYX/FAK/AKT pathway, which in turn impacts EMT and apoptosis.

Cobalt exposure and pulmonary function reduction in chronic obstructive pulmonary disease patients: the mediating role of club cell secretory protein.

BACKGROUND: Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). METHODS: All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. RESULTS: Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. CONCLUSION: Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

Photoinduced Radical Annulations of Tetrahydroisoquinoline Derivatives with 2-Benzothiazolimines: Highly Diastereoselective Synthesis of Fused Hexahydroimidazo[2,1-a]isoquinolines.

We report herein a photoinduced radical 1,3-dipolar cycloaddition between the 2-benzothiazolimines and tetrahydroisoquinoline derivatives with an organo-photocatalyst. A variety of benzothiazole-based hexahydroimidazo[2,1-a]isoquinoline architectures with great synthetic value were conveniently and efficiently constructed in moderate to good yields and excellent diastereoselectivities with highly tolerant functional groups. Moreover, the practicality and utility of this protocol were demonstrated by scale-up synthesis and facile elaboration. Preliminary mechanistic investigations indicated that the reaction proceeded via a visible-light-induced radical 1,3-dipolar cycloaddition pathway. This finding is expected to stimulate a more extensive exploration of the green and concise synthesis of structurally diverse heterocyclic molecules in the synthetic community.

Performance of the Aspergillus galactomannan lateral flow assay with a digital reader for the diagnosis of invasive aspergillosis: a multicenter study.

PURPOSE: The objective of this multicenter study was to compare the diagnostic performance of lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) to detect the Dynamiker Aspergillus Galactomannan levels in serum and bronchoalveolar lavage fluid (BALF) samples for I. METHODS: We registered 310 clinically suspected Aspergillus infection patients from December 2021 to February 2023 and classified them into subgroups as the "IA group" and "non-IA group" based on the latest EORTC/MSG guidelines. The immunoassays were analyzed by LFA and ELISA respectively. RESULTS: Galactomannan was examined using LFA, and serum and BALF samples demonstrated sensitivities of 82.57% and 89.47%, specificities of 90.76% and 92.00%, PPVs of 89.11% and 96.23%, and NPVs of 85.04% and 79.31%, respectively. Galactomannan was observed using two assays in serum and BALF samples and showed PPAs of 95.11% and 93.33%, NPAs of 89.19% and 96.30%, and TPAs of 92.47% and 94.25%, respectively. The ROC curve demonstrated that LFA had optimum diagnostic value when the index value (I value) = 0.5, the sensitivity was 84.94%, and the specificity was 90.97%. CONCLUSION: Compared to the ELISA method, the LFA has shown excellent performance for the diagnosis of IA in serum and BALF sample and can be used as an assay for the early diagnosis of patients with IA. The dynamic change in galactomannan levels may be useful for assessing treatment response.

Effect and mechanism of needleless transcutaneous neuromodulation on gastrointestinal function after pancreaticoduodenectomy.

BACKGROUND: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. METHODS: A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. RESULTS: 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(ß = - 0.349, p = 0.035). CONCLUSION: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.

Identification of COP9 signalosome (CSN) subunits and antiviral function analysis of CSN5 in shrimp.

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) typically composing of eight subunits (CSN1-8) mediates the process of deneddylation and deubiquitination. The fifth subunit of COP9 signalosome, CSN5, has special characteristics compared with the other seven subunits, and plays vital roles in the deneddylation activity and diverse cellular processes. However, the role of CSN5 in antiviral immunity is not clear. In this study, we identified 8 subunits (CSN1-8) of COP9 signalosome in shrimp Marsupenaeus japonicus. CSN1-6 were existed in all tested tissues, but CSN7-CSN8 were not detected in hepatopancreas. After WSSV challenged, the expression level of Csn1 to Csn4, and Csn6 to Csn8 were highly decreased, but the expression level of Csn5 was conspicuously increased in shrimp challenged by white spot syndrome virus (WSSV). The CSN5 was recombinantly expressed in Escherichia coli and its polyclonal antibody was prepared. The expression level of CSN5 was conspicuously increased at RNA and protein levels in the shrimp challenged by WSSV. After knockdown of Csn5 by RNA interference, the WSSV replication was obviously increased in shrimp. When injected the recombinant protein of CSN5 with the membrane penetrating peptide into shrimp, WSSV replication was inhibited and the survival rate of shrimp was significantly improved compared with control. We further analyzed the expression of antimicrobial peptides (AMPs) in Csn5-RNAi shrimp, and the results showed that the expression of several AMPs was declined significantly. These results indicate that CSN5 inhibits replication of WSSV via regulating expression of AMPs in shrimp, and the recombinant CSN5 might be used in shrimp aquaculture for the white spot syndrome disease control.

Small mass limit for stochastic interacting particle systems with Lévy noise and linear alignment force.

We study the small mass limit in mean field theory for an interacting particle system with non-Gaussian Lévy noise. When the Lévy noise has a finite second moment, we obtain the limit equation with convergence rate ε+1/εN, by taking first the mean field limit N→∞ and then the small mass limit ε→0. If the order of the two limits is exchanged, the limit equation remains the same but has a different convergence rate ε+1/N. However, when the Lévy noise is α-stable, which has an infinite second moment, we can only obtain the limit equation by taking first the small mass limit and then the mean field limit, with the convergence rate 1/Nα-1+1/Np2+εp/α where p∈(1,α). This provides an effectively limit model for an interacting particle system under a non-Gaussian Lévy fluctuation, with rigorous error estimates.

Prenylated Acetophenone Derivatives from the Leaves of Acronychia pedunculata and Their Anti-proliferative Activities.

Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.

Extent and Resistance Patterns of Gram-negative Bacteria Isolated From 13 Hospitals in Shaoxing, Zhejiang Province.

Gram-negative bacteria are increasingly recognized as the sauce of severe infections. In recent years, epidemiological data has indicated that the drug resistance rate of Gram-negative bacteria has significantly increased. We analyzed the epidemiological surveillance data of gram-negative bacteria in Shaoxing City in 2021 by retrospectively collecting drug susceptibility data of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Burkholderia cepacian from thirteen tertiary hospitals. A total of 24,142 strains were collected from thirteen hospitals. The isolation rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, P. mirabilis, E. cloacae, and B. cepacian were 29.25%, 18.83%, 11.03%, 8.43%, 3.80%, 3.12%, and 0.75%, respectively. Among them, 2.86% were carbapenem-resistant E. coli, 12.98% were CRKP, 31.27% were CRPA, and 34.77% were CRAB. Carbapenem-resistant Enterobacterales were more sensitive to ceftazidime-avibactam and polymyxin. The drug resistance rates of P. aeruginosa and A. baumannii to polymyxin were 0 and 1.3%, but the resistance rates to ceftazidime-avibactam were 10.5% and 26.0%, respectively. Based on results from epidemiological data, CRKP had a high isolation rate and non-fermenting bacteria had a high resistance rate to ceftazidime-avibactam. All hospitals should strengthen monitoring and enact continuous intervention to reduce the generation and spread of drug-resistant bacteria.

Sirtuin 1 Inhibits Fatty Acid Synthesis through Forkhead Box Protein O1-Mediated Adipose Triglyceride Lipase Expression in Goat Mammary Epithelial Cells.

Sirtuin 1 (SIRT1) is a key upstream regulator of lipid metabolism; however, the molecular mechanisms by which SIRT1 regulates milk fat synthesis in dairy goats remain unclear. This study aimed to investigate the regulatory roles of SIRT1 in modulating lipid metabolism in goat mammary epithelial cells (GMECs) and its impact on the adipose triglyceride lipase (ATGL) promoter activity using RNA interference (RNAi) and gene overexpression techniques. The results showed that SIRT1 is significantly upregulated during lactation compared to the dry period. Additionally, SIRT1 knockdown notably increased the expressions of genes related to fatty acid synthesis (SREBP1, SCD1, FASN, ELOVL6), triacylglycerol (TAG) production (DGAT2, AGPAT6), and lipid droplet formation (PLIN2). Consistent with the transcriptional changes, SIRT1 knockdown significantly increased the intracellular contents of TAG and cholesterol and the lipid droplet abundance in the GMECs, while SIRT1 overexpression had the opposite effects. Furthermore, the co-overexpression of SIRT1 and Forkhead box protein O1 (FOXO1) led to a more pronounced increase in ATGL promoter activity, and the ability of SIRT1 to enhance ATGL promoter activity was nearly abolished when the FOXO1 binding sites (FKH1 and FKH2) were mutated, indicating that SIRT1 enhances the transcriptional activity of ATGL via the FKH element in the ATGL promoter. Collectively, our data reveal that SIRT1 enhances the transcriptional activity of ATGL through the FOXO1 binding sites located in the ATGL promoter, thereby regulating lipid metabolism. These findings provide novel insights into the role of SIRT1 in fatty acid metabolism in dairy goats.

Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture.

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.

Zincophilic Sites Enriched Hydrogen-bonded Organic Framework as Multifunctional Regulating Interfacial Layers for Stable Zinc Metal Batteries.

To construct an efficient regulating layer for Zn anodes that can simultaneously address the issues of dendritic growth and side reactions is highly demanded for stable zinc metal batteries (ZMBs). Herein, we fabricate a hydrogen-bonded organic framework (HOF) enriched with zincophilic sites as a multifunctional layer to regulate Zn anodes with controlled spatial ion flux and stable interfacial chemistry (MA-BTA@Zn). The framework with abundant H-bonds helps capture H2O and remove the solvated shells on [Zn(H2O)6]2+, leading to suppressed side reactions. The HOF layer also helps form electrolyte-philic surfaces and expose Zn (002) crystal planes which benefit for rapid conduction and uniform deposition of Zn2+, and weakened sides reactions. Additionally, the electrochemically active zincophilic sites (C=O, -NH2 and triazine groups) favor the targeted guidance and penetration of Zn2+ and provide advantageous sites for uniform Zn deposition. High Young's modulus of the HOF layer further contributes to a high interfacial flexibility and stability against Zn plating-associated stress. The MA-BTA@Zn symmetric cells thereby obtain a substantially extended battery life over 1000 h at 4 mA cm-2. The MA-BTA@Zn||Cu half-cell demonstrates a highly reversible Zn stripping/plating process over 1500 cycles with impressive average Coulombic efficiency (CE) of 99.5% at 10 mA cm-2.

Intercellular adhesion molecule 2 as a novel prospective tumor suppressor induced by ERG promotes ubiquitination-mediated radixin degradation to inhibit gastric cancer tumorigenicity and metastasis.

BACKGROUND: Gastric cancer (GC) is a fatal cancer with unclear pathogenesis. In this study, we explored the function and potential mechanisms of intercellular adhesion molecule 2 (ICAM2) in the development and advancement of GC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to quantify ICAM2 expression in harvested GC tissues and cultured cell lines. Immunohistochemical analyses were conducted on a GC tissue microarray to quantify ICAM2 expression and explore its implication on the prognosis of GC patients. In vitro experiments were carried out to reveal the biological functions of ICAM2 in GC cell lines. Further, in vivo experiments were conducted using xenograft models to assess the impact of ICAM2 on GC development and metastasis. Western blot, immunofluorescence, immunoprecipitation, luciferase assay, chromatin immunoprecipitation, and ubiquitination analysis were employed to investigate the underlying mechanisms. RESULTS: ICAM2 expression was downregulated in GC, positively correlating with advanced T stage, distant metastasis, advanced clinical stage, vessel invasion, and shorter patient survival time. ICAM2 overexpression suppressed the proliferation, migration, invasion, metastasis of GC cells as well as their ability to form tumors, whereas ICAM2 knockdown yielded opposite results. Erythroblast transformation-specific-related gene (ERG) as a transcription factor promoted the transcription of ICAM2 by binding to the crucial response element localized within its promoter region. Further analysis revealed that ICAM2 reduced radixin (RDX) protein stability and expression. In these cells, ICAM2 bound to the RDX protein to promote the ubiquitination and degradation of RDX via NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L), and this post-translational modification resulted in the inhibition of GC. CONCLUSIONS: In summary, this study demonstrates that ICAM2, which is induced by ERG, suppresses GC progression by enhancing the ubiquitination and degradation of RDX in a NEDD4L-dependent manner. Therefore, these results suggest that ICAM2 is a potential prognostic marker and a therapeutic target for GC.

miR-1273h-5p protects the human corneal epithelium against UVR-induced oxidative stress and apoptosis: Role of miR-1273h-5p in climatic droplet keratopathy.

Climatic droplet keratopathy (CDK) is characterized by an increased number of oil-like deposits on the most anterior corneal layers, which affect vision and can cause blindness. Environmental ultraviolet radiation (UVR) exposure is a major risk factor, but the underlying mechanism of CDK pathogenesis is unclear. Increasing evidence has demonstrated that miRNAs participate in the cross-talk with oxidative stress. We aimed to explore whether certain miRNAs are involved in the pathogenesis of CDK. We performed miRNA sequencing of tears from patients with CDK and healthy individuals from Tacheng region of Xinjiang and conducted bioinformatic analysis of key miRNAs. We also evaluated viability, migration, and apoptosis of human corneal epithelial cells (HCECs) subjected to UVR treatment. miR-1273h-5p expression was abnormally downregulated in the tears of patients with CDK. miR-1273h-5p promoted cell proliferation and migration and inhibited UVR-induced mitochondrial apoptosis. miR-1273h-5p protected HCECs against UVR-induced oxidative damage by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial apoptosis via the activation of the Nrf2 pathway. Thus, our results suggest that miR-1273h-5p protects the corneal epithelium against UVR-induced oxidative stress damage.