Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies.

OBJECTIVE: The human cluster of differentiation (CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer (NK) cells targeting hematologic malignancies (HMs). METHODS: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine (PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients. RESULTS: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS-CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an "exhausted" phenotype of intratumoral NK cells in patients with HMs or solid tumors. CONCLUSIONS: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a poor prognosis, and the efficacy of current therapeutic strategies is extremely limited in advanced diseases. Our previous study reported that protein tyrosine phosphatase receptor epsilon (PTPRE) is a promoting factor in HCC progression. In this study, our objective was to evaluate the treatment effect of PTPRE inhibitors in different HCC preclinical models. Our results indicated that the PTPRE inhibitory compound 63 (Cpd-63) inhibited tumor cell proliferation, migration, and HCC organoid growth. Mechanism research revealed that Cpd-63 could inhibit the expression of MYC and MYC targets by inhibiting the activation of SRC. Additionally, we found that Cpd-63 could improve the response of sorafenib in HCC cells. In conclusion, we demonstrated that the PTPRE inhibitors represented a potential therapeutic agent for HCC management.

Facile fabrication of adenosine triphosphate/chitosan/polyethyleneimine coating for high flame-retardant lyocell fabrics with outstanding antibacteria.

Addressing highly flammable and easily breeding bacteria property via environmentally friendly approach was critical for the large-scale application of lyocell fibers. Herein, a bio-based coating constructed by layer-by-layer deposition of adenosine triphosphate (ATP), chitosan (CS), and polyethyleneimine (PEI) was successfully fabricated to obtain excellent fire-resistant and antimicrobial lyocell fabrics (LBL/Lyocell). The resulted fabrics with add-on of 11.5 wt% achieved the limiting oxygen index (LOI) of 32.0 %. Meanwhile, compared with the pure lyocell fabrics, the peak of heat release rate (PHRR), total heat release (THR), and fire growth rate (FIGRA) of LBL/Lyocell fabrics decreased by 75.2 %, 61.0 % and 69.8 % in cone calorimetric test (CCT), respectively. By characterizing the gaseous products and solid residues, the presence of the ATP/CS/PEI coating could not only quickly form the dense expanded carbon layer by itself, but also promote the conversion of cellulose into thermal-stability residues, thus reducing the release of combustible substances during combustion and protecting the lyocell fabrics. In addition, LBL/Lyocell showed excellent antimicrobial properties with 99.99 % antibacterial rates against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This bio-based coating was a promising candidate for efficiently flame-retardant cellulose fibers with excellent antibacteria.

The Protective Effect of Auricularia cornea var. Li. Polysaccharide on Alcoholic Liver Disease and Its Effect on Intestinal Microbiota.

This study's objective was to examine the protective effect and mechanism of a novel polysaccharide (AYP) from Auricularia cornea var. Li. on alcoholic liver disease in mice. AYP was extracted from the fruiting bodies of Auricularia cornea var. Li. by enzymatic extraction and purified by DEAE-52 and Sephacryl S-400. Structural features were determined using high-performance liquid chromatography, ion exchange chromatography and Fourier-transform infrared analysis. Additionally, alcoholic liver disease (ALD) mice were established to explore the hepatoprotective activity of AYP (50, 100 and 200 mg/kg/d). Here, our results showed that AYP presented high purity with a molecular weight of 4.64 × 105 Da. AYP was composed of galacturonic acid, galactose, glucose, arabinose, mannose, xylose, rhamnose, ribos, glucuronic acid and fucose (molar ratio: 39.5:32.9:23.6:18.3:6.5:5.8:5.8:3.3:2:1.1). Notably, AYP remarkably reduced liver function impairment (alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC)), nitric oxide (NO) and malondialdehyde (MDA) of the liver and enhanced the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (gGSH)) in mice with ALD. Meanwhile, the serum level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were reduced in ALD mice treated by AYP. Furthermore, the AYPH group was the most effective and was therefore chosen to further investigate its effect on the intestinal microbiota (bacteria and fungi) of ALD mice. Based on 16s rRNA and ITS-1 sequencing data, AYP influenced the homeostasis of intestinal microbiota to mitigate the damage of ALD mice, possibly by raising the abundance of favorable microbiota (Muribaculaceae, Lachnospiraceae and Kazachstania) and diminishing the abundance of detrimental microbiota (Lactobacillus, Mortierella and Candida). This discovery opens new possibilities for investigating physiological activity in A. cornea var. Li. and provides theoretical references for natural liver-protecting medication research.

Facile construction of bio-based high fire-safety cellulose fabrics with well wearing performance.

The design of flame-retardant cellulose fabrics suffered from deterioration on wearing performance and environmental issue. Here, we developed facile construction of bio-based high fire-safety cellulose fabrics (lyocell) that exploited the bio-based flame-retardant coating (APD) by adenosine triphosphate (ATP) and dicyandiamide (DCD) via ionic reaction. The rich phosphorus/nitrogen elements of APD enabled the excellent fire safety of APD/Lyocell. Specifically, the APD/Lyocell2 had a higher limiting oxygen index (LOI) value of 29.3 %, a lower peak of heat release rate (PHRR, decreasing by 66.6 %), and a reduced total heat rate (THR, lowered by 56.5 %) with respect to pure lyocell fabrics. Interestingly, the APD/Lyocell2 exhibited well flame-retardant durability via passing the vertical burning test after 100 rubs. The satisfactory flame-retardant behaviors of APD/Lyocell derived from the excellent synergistic effect on the gaseous-solid phases, where APD could release more non-flammable gasses and generate phosphoric acid, polyphosphoric acid, etc. to accelerate itself and cellulose dehydration into char residues during combustion. More importantly, the wearing performance of APD/Lyocell fabrics, such as handle, air permeability and tensile strength, etc. almost remained after treatment. The ease of operation and use of bio-based coating made it a promising option to obtain the practical lyocell fabrics with flame-retardancy.

Self-driven immune checkpoint blockade and spatiotemporal-sensitive immune response monitoring in acute myeloid leukemia using an all-in-one turn-on bionanoprobe.

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.

Hepatocyte TIPE2 is a fasting-induced Raf-1 inactivator that drives hepatic gluconeogenesis to maintain glucose homeostasis.

BACKGROUND: The liver regulates metabolic balance during fasting-feeding cycle. Hepatic adaptation to fasting is precisely modulated on multiple levels. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immunity that reduces several liver pathologies, but its physiological roles in hepatic metabolism are largely unknown. METHODS: TIPE2 expression was examined in mouse liver during fasting-feeding cycle. TIPE2-knockout mice, liver-specific TIPE2-knockout mice, liver-specific TIPE2-overexpressed mice were examined for fasting blood glucose and pyruvate tolerance test. Primary hepatocytes or liver tissues from these mice were evaluated for glucose production, lipid accumulation, gene expression and regulatory pathways. TIPE2 interaction with Raf-1 and TIPE2 transcription regulated by PPAR-α were examined using gene overexpression or knockdown, co-immunoprecipitation, western blot, luciferase reporter assay and DNA-protein binding assay. RESULTS: TIPE2 expression was upregulated in fasted mouse liver and starved hepatocytes, which was positively correlated with gluconeogenic genes. Liver-specific TIPE2 deficiency impaired blood glucose homeostasis and gluconeogenic capacity in mice upon fasting, while liver-specific TIPE2 overexpression elevated fasting blood glucose and hepatic gluconeogenesis in mice. In primary hepatocytes upon starvation, TIPE2 interacted with Raf-1 to accelerate its ubiquitination and degradation, resulting in ERK deactivation and FOXO1 maintenance to sustain gluconeogenesis. During prolonged fasting, hepatic TIPE2 deficiency caused aberrant activation of ERK-mTORC1 axis that increased hepatic lipid accumulation via lipogenesis. In hepatocytes upon starvation, PPAR-α bound with TIPE2 promoter and triggered its transcriptional expression. CONCLUSIONS: Hepatocyte TIPE2 is a PPAR-α-induced Raf-1 inactivator that sustains hepatic gluconeogenesis and prevents excessive hepatic lipid accumulation, playing beneficial roles in hepatocyte adaptation to fasting.

States of contra-lateral rotator cuff - Based on bilateral shoulder ultrasound results of 401 patients.

BACKGROUND: For patients with rotator cuff tear (RCT), the contra-lateral shoulders have higher risk of RCT than general population. It has been proved by several previous studies. The focus of this study is to obtain the data of contra-lateral rotator cuff tear in Chinese population, and to find the rules of contra-lateral rotator cuff tear through statistical analysis. METHODS: From March 2016 to January 2020, patients who underwent shoulder arthroscopic surgery were included in the study, we conduct bilateral shoulder ultrasound before surgery, patients information collection include gender, age, occupation and whether received contra-lateral rotator cuff surgery within 1-3 years. The above information was statistically analyzed. RESULTS: According to the inclusion and exclusion criteria, 401 patients were included. The incidence of contra-lateral rotator cuff tear was 24.3%, 5.58% of them underwent contra-lateral rotator cuff repair surgery within 3 years. The degree of contra-lateral rotator cuff tear was positively correlated with the degree of the primary side; Patients with full-thickness rotator cuff tear were more likely to have contra-lateral rotator cuff tear than patients with partial rotator cuff tear. For patients with supraspinatus tendon tear, the contra-lateral rotator cuff tear risk increases, For patients with subscapularis muscle tear, the contra-lateral rotator cuff tear risk doesn't increases. Contra-lateral rotator cuff tear is related to age, the risk of contra-lateral rotator cuff tear is higher in elderly patients. CONCLUSIONS: The contra-lateral RCT data obtained in our study was 24.3%, significantly lower than that of previous studies. The reasons may include ethnic variation, lifestyle, and proportion of heavy physical labor. The condition of contra-lateral rotator cuff is closely related to affected side rotator cuff tear.

CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue.

Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.

Application of Tranexamic Acid in Shoulder Arthroscopic Surgery: A Randomised Controlled Trial.

Objective To explore the optimal administration route of tranexamic acid (TXA) in shoulder arthroscopic surgery. Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups: control group (without TXA treatment), intravenous group (TXA was intravenously administered 10 minutes before surgery), irrigation group (TXA was added to the irrigation fluid during subacromial decompression and acromioplasty), and intravenous plus irrigation group (TXA was applied both intravenously and via intra-articular irrigation). The primary outcome was visual clarity assessed with visual analog scale (VAS) score, and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure. Results There were 134 patients enrolled in the study, including 33 in the control group, 35 in the intravenous group, 32 in the irrigation group, and 34 in the intravenous plus irrigation group. The median and interquartile range of VAS scores for the intravenous, irrigation, and intravenous plus irrigation groups were 2.70 (2.50, 2.86) (Z = -3.677, P = 0.002), 2.67 (2.50, 2.77) (Z = -3.058, P < 0.001), and 2.91 (2.75, 3.00) (Z = -6.634, P < 0.001), respectively, significantly higher than that of the control group [2.44 (2.37, 2.53)]. Moreover, the control group consumed more irrigation fluid than the intravenous group, irrigation group, and intravenous plus irrigation group (all P < 0.05). The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group (both P < 0.001). There was no difference in subacromial decompression and acromioplasty operative time among the four groups. Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity, and the combined application is more effective.

Recent advances in engineering hydrogels for niche biomimicking and hematopoietic stem cell culturing.

Hematopoietic stem cells (HSCs) provide a life-long supply of haemopoietic cells and are indispensable for clinical transplantation in the treatment of malignant hematological diseases. Clinical applications require vast quantities of HSCs with maintained stemness characteristics. Meeting this demand poses often insurmountable challenges for traditional culture methods. Creating a supportive artificial microenvironment for the culture of HSCs, which allows the expansion of the cells while maintaining their stemness, is becoming a new solution for the provision of these rare multipotent HSCs. Hydrogels with good biocompatibility, excellent hydrophilicity, tunable biochemical and biophysical properties have been applied in mimicking the hematopoietic niche for the efficient expansion of HSCs. This review focuses on recent progress in the use of hydrogels in this specialized application. Advanced biomimetic strategies use for the creation of an artificial haemopoietic niche are discussed, advances in combined use of hydrogel matrices and microfluidics, including the emerging organ-on-a-chip technology, are summarized. We also provide a brief description of novel stimulus-responsive hydrogels that are used to establish an intelligent dynamic cell microenvironment. Finally, current challenges and future perspectives of engineering hydrogels for HSC biomedicine are explored.

PVA-SM microstructure enhanced ratiometric fluorescence probe for formaldehyde detection in solution and gas.

Formaldehyde (FA) is one of the most common pollutants, which has tremendous harm to humans and environment. In this work, 4-amino-3-pentene-2-one (Fluoral-p) and SiO2 coated quantum dot (QD@SiO2) were combined to implement a new ratiometric fluorescence probe QD@SiO2-Fluoral-p for FA detection. In addition, by utilization of polyvinyl alcohol (PVA) and SiO2 microsphere (SM), a kind of PVA-SM microstructure was assembled with QD@SiO2-Fluoral-p to composite a signal enhanced sensing film. The QD@SiO2-Fluoral-p exhibited good response to 0-400 mg/L FA solution and an enhancement around 15 folds was realized after introducing PVA-SM. In both situations, the probe showed linear relationship to FA concentration (CFA), with detection limits of 14 and 0.5 mg/L, respectively. Also, the sensing film showed a good linear response to FA gas in the range of 0 to 2 ppm, with a detection limit 0.03 ppm. As a result, the PVA-SM enhanced ratiometric fluorescence probe features high sensitivity, low detection limit, good selectivity, as well as portable, which can serve as a useful tool for investigating FA in solution and gas at room temperature.

Treatment of posterolateral tibial plateau fractures with a rotational support plate and special pressurizer: technical note and retrospective case series.

BACKGROUND: In tibial plateau fractures, the posterolateral segment of the tibia plateau is frequently affected and challenging to treat. Although there are many surgical approaches and fixation methods for the treatment of these fractures, all of these methods have limitations. We designed a new rotational support plate (RSP) and a special pressurizer that can fix the fracture directly via the anterolateral approach. This method is advantageous because it leads to little trauma, involves a simple operation, and has a reliable fixation effect. This study details the technique of treating these fractures with the RSP and special pressurizer and provides the outcomes. METHODS: From May 2016 to January 2019, the data of 12 patients with posterolateral tibial plateau fractures treated with the RSP and special pressurizer in our hospital were retrospectively analyzed. Postoperative rehabilitation was advised, knee X-rays were taken at follow-ups, and fracture healing, complications, and knee range of motion were assessed. The Hospital for Special Surgery (HSS) knee score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to evaluate knee function at the last follow-up. RESULTS: The average follow-up time of all patients was 16.5 months (range, 12-25 months). The average bony union time was 3.2 months (range, 3-4.5 months). At the last follow-up, the average knee range of motion was 138° (range, 107-145°). The average HSS score was 91 (range, 64-98). The average KOOS Symptoms score was 90 (range, 75-96). The average KOOS Pain score was 91 (range, 72-97). The average KOOS ADL score was 91 (range, 74-97). The average KOOS sport/recreation score was 83 (range, 70-90). The average KOOS QOL score was 88 (range, 69-93). Skin necrosis, incision infections, and fixation failure did not occur during the follow-up period. CONCLUSIONS: With our newly designed RSP and special pressurizer, posterolateral tibial plateau fractures can be easily and effectively reduced and fixed through the anterolateral approach, which serves as a novel treatment for posterolateral tibial plateau fractures.

Development of a Digital Patient Education Tool for Patients With Cancer During the COVID-19 Pandemic.

BACKGROUND: Due to the COVID-19 pandemic, a large portion of oncology consultations have been conducted remotely. The maladaptation or compromise of care could negatively impact oncology patients and their disease management. OBJECTIVE: We aimed to describe the development and implementation process of a web-based, animated patient education tool that supports oncology patients remotely in the context of fewer in-person interactions with health care providers. METHODS: The platform created presents multilingual oncology care instructions. Animations concerning cancer care and mental health during the COVID-19 pandemic as well as immunotherapy and chemotherapy guides were the major areas of focus and represented 6 final produced video guides. RESULTS: The videos were watched 1244 times in a period of 6 months. The most watched animation was the COVID-19 & Oncology guide (viewed 565 times), followed by the video concerning general treatment orientations (viewed 249 times) and the video titled "Chemotherapy" (viewed 205 times). Although viewers were equally distributed among the age groups, most were aged 25 to 34 years (342/1244, 27.5%) and were females (745/1244, 59.9%). CONCLUSIONS: The implementation of a patient education platform can be designed to prepare patients and their caregivers for their treatment and thus improve outcomes and satisfaction by using a methodical and collaborative approach. Multimedia tools allow a portion of a patient's care to occur in a home setting, thereby freeing them from the need for hospital resources.

WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemias (T-ALLs) are aggressive and heterogeneous hematologic tumors resulting from the malignant transformation of T-cell progenitors. The major challenges in the treatments of T-ALL are dose-limiting toxicities of chemotherapeutics and drug resistance. Despite important progress in deciphering the genomic landscape of T-ALL, translation of these findings into effective targeted therapies remains largely unsuccessful. New targeted agents with significant antileukemic efficacy and less toxicity are in urgent need. We herein report that the expression of WEE1, a nuclear tyrosine kinase involved in cell cycle G2-M checkpoint signaling, is significantly elevated in T-ALL. Mechanistically, oncogenic MYC directly binds to the WEE1 promoter and activates its transcription. T-ALL cells particularly rely on the elevated WEE1 for cell viability. Pharmacological inhibition of WEE1 elicits global metabolic reprogramming which results in a marked suppression of aerobic glycolysis in T-ALL cells, leading to an increased dependency on glutaminolysis for cell survival. As such, dual targeting of WEE1 and glutaminase (GLS1) induces synergistic lethality in multiple T-ALL cell lines and shows great efficacy in T-ALL patient-derived xenografts. These findings provide mechanistic insights in the regulation of WEE1 kinase in T-ALL and suggest an additional vulnerability during WEE1 inhibitor treatments. In aggregate, we highlight a promising combination strategy of dual inhibition of cell cycle kinase and metabolic enzymes for T-ALL therapeutics.

Synergistic targeting of CHK1 and mTOR in MYC-driven tumors.

Deregulation of v-myc avian myelocytomatosis viral oncogene homolog (MYC) occurs in a broad range of human cancers and often predicts poor prognosis and resistance to therapy. However, directly targeting oncogenic MYC remains unsuccessful, and indirectly inhibiting MYC emerges as a promising approach. Checkpoint kinase 1 (CHK1) is a protein kinase that coordinates the G2/M cell cycle checkpoint and protects cancer cells from excessive replicative stress. Using c-MYC-mediated T-cell acute lymphoblastic leukemia (T-acute lymphoblastic leukemia) and N-MYC-driven neuroblastoma as model systems, we reveal that both c-MYC and N-MYC directly bind to the CHK1 locus and activate its transcription. CHIR-124, a selective CHK1 inhibitor, impairs cell viability and induces remarkable synergistic lethality with mTOR inhibitor rapamycin in MYC-overexpressing cells. Mechanistically, rapamycin inactivates carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), the essential enzyme for the first three steps of de novo pyrimidine synthesis, and deteriorates CHIR-124-induced replicative stress. We further demonstrate that dual treatments impede T-acute lymphoblastic leukemia and neuroblastoma progression in vivo. These results suggest simultaneous targeting of CHK1 and mTOR as a novel and powerful co-treatment modality for MYC-mediated tumors.

Treatment of the tibial pilon fractures using the antero-medial fibula approach: Ten case series.

Pilon fractures are always results of the high-energy trauma. They are often accompanied with serious soft tissue injury, and tension blisters happened in most cases. For comminuted fractures and poor soft tissue, how to select the incision is challenging. This study aimed to explore the outcomes of the treatment of ten 43-B/C pilon fractures using an anteromedial fibula approach.Ten closed pilon fractures combined with fibula fractures were treated in our hospital from January 2015 to July 2016. Six cases were AO/OTA type 43-B and 4 cases were 43-C, including 9 males and 1 female with a mean age of 36.3 years (range: 20-60 years). When the skin wrinkled, all patients were treated by the senior authors with open reduction and internal fixation using an anteromedial fibula approach. Postoperatively, patients were followed up at 1 month, 3 months, 6 months, 12 months, and 18 months, respectively. The incision healing, the American Orthopedic Foot and Ankle Society scores and fracture healing were recorded to get a comprehensive evaluation of the effect for the incision.All patients were followed from 9 to 18 months (average: 14.1 months). Anatomic reduction was achieved in 7 cases and satisfactory in 3 cases by the Burwell-Charnley radiological criteria evaluation. All patients had complete retention of the dorsal extensor tendon sheath. The most incisions had a good healing without necrosis at 2 weeks after surgery except 1 case. The factures were healed at a range of 12 to 18 weeks (average: 13.7 ±â€Š1.2 weeks). The American Orthopedic Foot and Ankle Society scores were excellent in 7 cases and good in 3 cases at 1 year after surgery (average: 85.6 ±â€Š4.2 points). The satisfactory outcomes were achieved in most patients.The anteromedial fibula approach used for pilon fractures can lead to an effective exposure and allow fixation of tibia and fibula fractures with minimal soft tissue injury. It is a safe, simple, and effective approach that allows for satisfactory functional rehabilitation of the ankle joint. LEVEL OF EVIDENCE:: therapeutic Level IV.

Surface Plasmon-Enhanced Optical Formaldehyde Sensor Based on CdSe@ZnS Quantum Dots.

For the first time, a reproducible surface plasmon-enhanced optical sensor for the detection of gaseous formaldehyde was proposed, which was fabricated by depositing a mixture of CdSe@ZnS quantum dots (QDs), fumed silica (FS), and gold nanoparticles (GNs) on the surface of a silica sphere array to meet the urgent requirement of a rapid, sensitive, and highly convenient formaldehyde detection method. Because of the spectral overlap between QDs and GNs, plasmon-enhanced fluorescence was observed in the film of QDs/FS/GNs. When exposed to formaldehyde molecules, the enhanced fluorescence was quenched linearly with the increase of formaldehyde concentration in the range of 0.5-2.0 ppm. The reason is attributed to the nonradiative electron transfer from QDs to the carbonyl of formaldehyde molecules with the assistance of amino groups. Our results demonstrate that the designed sensors are capable of detecting ultralow concentration gaseous formaldehyde at room temperature with a fast response-recovery time and excellent selectivity, stability, and reproducibility. This work provides a simple and low-cost approach for optical formaldehyde sensor fabrication and shows promising applications in environmental detection.

Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis.

Deregulation of MYC plays an essential role in T cell acute lymphoblastic leukemia (T-ALL), yet the mechanisms underlying its deregulation remain elusive. Herein, we identify a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteracting GSK3ß-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1 (TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulated oncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradation concomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatory circuit that underlies T cell leukemogenesis, and provide a rationale for therapeutic targeting of oncogenic MYC via AURKB inhibition.

Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.

Activation of the NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome plays a key role in host immune response, which is the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages host cells, and therefore it must be precisely controlled. Here, we discover that Cullin1 (CUL1), a key component of the Skp1-Cullin1-F-box E3 ligase, plays a critical role in controlling the NLRP3 inflammasome. CUL1 represses inflammasome assembly in cultured cells, suppresses NLRP3 function in human monocytic cell line macrophages, and attenuates inflammatory responses in mouse model. Detailed studies demonstrate that CUL1 interacts with NLRP3 and promotes NLRP3 ubiquitination, but not protein degradation, to repress the NLRP3 inflammasome activation. Moreover, upon inflammatory stimuli, including ATP and nigericin treatments, CUL1 disassociates from NLRP3 to release the repression of the NLRP3 inflammasome. Thus, this study reveals a distinct and unique mechanism underlying the control of systematic activation of the NLRP3 inflammasome.-Wan, P., Zhang, Q., Liu, W., Jia, Y., Ai, S., Wang, T., Wang, W., Pan, P., Yang, G., Xiang, Q., Huang, S., Yang, Q., Zhang, W., Liu, F., Tan, Q., Zhang, W., Wu, K., Liu, Y., Wu, J. Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.