Long non-coding RNA KB-1460A1.5 promotes ferroptosis by inhibiting mTOR/SREBP-1/SCD1-mediated polyunsaturated fatty acid desaturation in glioma.

Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation of phospholipids and is related to cell metabolism, redox homeostasis and various signalling pathways related to cancer. The long non-coding RNA (lncRNA) KB-1460A1.5 acts as a tumour suppressor gene to regulate tumour growth in gliomas, but its molecular network regulatory mechanism is still unclear. In this study, we found that KB-1460A1.5 can induce ferroptosis in glioma and enhance sensitivity to RSL3, a ferroptosis inducer. Tandem mass tag proteomics and nontargeted metabolomics suggest that KB-1460A1.5 affects polyunsaturated fatty acid metabolic processes. Gas chromatography-mass spectrometry-based medium- and long-chain fatty acid-targeted metabolomics confirmed that upregulation of KB-1460A1.5 decreased the levels of monounsaturated fatty acids, oleic acid (OA) and palmitoleic acid (PO) in glioma cells. The addition of OA and PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, KB-1460A1.5 inhibited the mammalian target of rapamycin signalling pathway to suppress the expression of downstream sterol regulatory element-binding protein 1 (SREBP-1), thereby attenuating the stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation of polyunsaturated fatty acids. Finally, an animal model of subcutaneous glioma confirmed that KB-1460A1.5 could inhibit tumour progression, SREBP-1/SCD1 expression and ferroptosis. In conclusion, increasing the expression level of KB-1460A1.5 in glioma can promote the induction of oxidative stress and ferroptosis in cancer cells through SREBP-1/SCD1-mediated adipogenesis, demonstrating therapeutic potential in preclinical models.

Interfacial Behavior of Giant Amphiphiles Composed of Azobenzene and Polyhedral Oligomeric Silsesquioxane.

Giant amphiphiles containing azobenzene and polyhedral oligomeric silsesquioxane (POSS) units are synthesized by linking 4,4'-azodianiline (ADA) and POSS derivatives by stepwise amidation and further modification. The synthesized giant amphiphiles are photoresponsive and show trans-cis isomerization under ultraviolet (UV) irradiation. These giant amphiphiles are spread on the air-water interface and compressed by the barrier without and under UV irradiation. By compression, the giant amphiphiles undergo a phase transition from gas (G), liquid expanded (LE), liquid condensed (LC), and solid (S) to a final collapse on the water surface. The giant amphiphiles are cis-isomer-rich under UV irradiation and are trans-isomer-rich without UV irradiation. The trans-isomers are straight-shaped, while the cis-isomers are bent, and hence, their phase transition behaviors on the water surface exhibit a distinct difference.

Phase Behaviors of Giant Surfactants with Different Numbers of Fluorinated Polyhedral Oligomeric Silsesquioxane "Heads" and One Poly(ethylene oxide) "Tail" at the Air-Water Interface.

Giant surfactants with different numbers of aryl-trifluorovinyl ether-functionalized polyhedral oligomeric silsesquioxane (FVPOSS) heads and one poly(ethylene oxide) (PEO) tail, (FVPOSS)n-PEO227, are precisely synthesized. The phase behaviors of (FVPOSS)n-PEO227 at the air-water interface were investigated through surface pressure measurements (isotherm and hysteresis experiments) and the Brewster angle microscopy. Upon increasing the number of FVPOSS heads, the interfacial behaviors of these giant surfactants greatly change. More phase transitions occur during the compression as the number of FVPOSS heads increased from one to two and three. The evolution of morphologies of Langmuir films and compression-expansion hysteresis curves further illustrate phase transitions at the air-water interface. Furthermore, molecular mechanisms to describe phase transitions of (FVPOSS)n-PEO227 at the interface are put forward. This study deepens the understanding of interfacial phase behaviors of special giant surfactants and provides knowledge of nanostructure design and construction at the interface.

Finite Element Analysis of Femoral Neck Fracture Treated with Bidirectional Compression-Limited Sliding Screw.

BACKGROUND The rate of femoral neck shortening after internal fixation for femoral neck fracture is high and this complication reduces the function of the affected lower limb. The aim of this study was to design a bidirectional compression-limited sliding screw (BCLSC) that can achieve a full balance between retaining the sliding pressure of the ends of and maintaining the length of the femoral neck. MATERIAL AND METHODS We constructed a 3-dimensional model of a Pauwels III femoral neck fracture and models of 3 internal fixation methods (3 cannulated screws [3CS], dynamic hip screw [DHS]+CS, and BCLSC) by finite element analysis (FEA).The finite element model simulated the loading of the human body when standing on 1 leg. Displacement and stress distribution of the models were calculated based on an axial stress of 600 N. RESULTS The peak von Mises stress (VMS) values of fracture ends in the 3CS, DHS+CS and BCLSC groups were 94.687 MPa, 26.375 MPa and 45.698 MPa; the peak VMS values of internal fixed stress were 451.53 MPa, 174.45 MPa, and 337.34 MPa; the peak VMS values of the lateral femoral wall were 70.021 MPa, 53.033 MPa, and 20.009 MPa; maximum displacements of the femoral head were 1.4482 mm, 1.3813 mm, and 1.3889 mm; and the internal fixed displacement peaks were 4.1134 mm, 3.91 mm, and 4.1004 mm, respectively. CONCLUSIONS The FEA showed that compared with the CS, the new BCLSC showed better performance in resisting shearing force for Pauwels III femoral neck fracture, with better mechanical properties. These data provide a basis for further experiments and clinical application.

Flavonoid derivatives synthesis and anti-diabetic activities.

In high fat diet-induced obese mice, the flavonoid derivative of tiliroside, Fla-CN, has antihyperglycemic effects, can improve insulin sensitivity, ameliorate metabolic lipid disorders, and benefits certain disorders characterized by insulin resistance. Fla-CN is a novel lead compound to discovery anti-diabetic and anti-obesity drugs. The present study reported the optimization of Fla-CN to obtain a new derivative, 10b, which has improved glucose consumption at the nanomolar level (EC50 = 0.3 nM) in insulin resistant (IR) HepG2 cells. 10b also increased the glycogen content and glucose uptake, and concurrently inhibited gluconeogenesis in HepG2 cells. Western blotting showed that 10b markedly enhanced the phosphorylation of AMPK (AMP-activated protein kinase) and AS160 (protein kinase B substrate of 160 kDa) and reduced the levels of the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) and G6P (glucose 6-phosphatase) in HepG2 cells. The potential molecular mechanism of 10b may be activation of the AMPK/AS160 and AMPK/PEPCK/G6P pathways. We concluded that 10b might be a valuable candidate to discover anti-diabetic drugs.

'Y'-Shaped Palmar Common Digital Artery Interposition Bypass in the Treatment of an Infantile M2 Large Aneurysm and Literature Review.

OBJECTIVE: Both craniotomy and interventional embolization are difficult and risky to treat complex middle cerebral artery (MCA) aneurysms in infants. Trapping with revascularization is a therapeutic option for giant aneurysms that cannot be clipped or coiled alone. METHOD: We describe a technical method using revascularization with a natural Y-shaped palmar common digital artery interposition graft that provides a normal variation for a complex MCA aneurysm in an infant with intracerebral hemorrhage at 37 days of age. Conservative treatment was performed at that time. Seven months later, the patient was re-admitted to the hospital and was confirmed a large aneurysm in the M2 segment of the right MCA by cerebral angiography. A natural artery palmar common digital artery Y-graft was used as the graft and anastomosed to the M2 and both M3 trunks. RESULT: The symptoms improved after surgery, and the mRS score of the patient was 1 after 5 years of follow-up. CONCLUSION: The palmar common digital artery can be an option for intracranial revascularization bypass in complex intracranial aneurysms.

Design and Application of an Acetabular Integrative Anatomic Plate: A Retrospective Study of 178 Cases with Complex Acetabular Fractures.

OBJECTIVE: As conventional plates require repeated pre-bending during surgery with poor matching, this study aimed to explore the design and application of an acetabular integrative anatomical plate (AIAP) via the lateral-rectus approach (LRA) in fresh complex acetabular fractures for the good reduction and fixation. METHODS: We designed an AIAP based on the anatomical morphology of the Chinese people. From March 2016 to September 2021, 178 patients with fresh complex acetabular fractures treated with an AIAP via the LRA were retrospectively analyzed. All patients were treated by the LRA under general anesthesia in a supine position. The fragments were well reduced and fixed by AIAPs. The operation time and intraoperative blood loss were recorded. All patients underwent reexamination of pelvic X-rays and CT scans and were followed up for over 1 year postoperatively. The reduction quality of fracture was evaluated according to the Matta criteria. The postoperative functional recovery was evaluated by modified Merle d'Aubigne-Postel scoring system. Statistics were analyzed by SPSS 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS: All 178 patients went through the operation successfully. The time from injury to operation ranged from 5 to 21 days (8.7 ± 2.6 days). The operation time ranged from 35 to 150 min (75 ± 29 min). The intraoperative blood loss was from 250 to 1400 ml (440 ± 153 ml). According to the Matta score, the fracture reduction was evaluated as excellent in 131 cases, good in 31 cases, and poor in 16 cases, with an overall excellent and good rate of 91%. Four patients suffered wound fat liquefaction and healed after fresh dressing. All patients were followed up for 1 to 5 years without wound infection. All fractures were healed. At the last follow-up, the modified Merle d'Aubigne-Postel score results were evaluated as excellent in 125 cases, good in 26 cases, and fair in 27 cases, with an overall excellent and good rate of 84.8%. Postoperative complications included six cases of traumatic arthritis of the hips and two cases of femoral head necrosis. CONCLUSION: The LRA with an AIAP can help expose, reduce, and fix anterior and posterior columns as well as the quadrilateral area of the acetabulum, which is capable of improving the reduction quality of complex acetabular fractures and shortening surgical time and blood loss, thus reaching a good clinical efficacy.

Improving the Function of Meningeal Lymphatic Vessels to Promote Brain Edema Absorption after Traumatic Brain Injury.

Brain edema is the most common and fatal complication after traumatic brain injury (TBI). Meningeal lymphatic vessels (MLVs) are the conduits that transport cerebrospinal fluid (CSF) and macromolecules to deep extracranial cervical lymph nodes (dCLNs). After TBI, the drainage function of MLVs can become impaired. However, the scenario in which the improvement of the function of MLVs can promote brain edema absorption after TBI has not been reported. Therefore, the purpose of this study was to investigate the effects of ketoprofen, 9-cis retinoic acid (RA) and vascular endothelial cell growth factor-C (VEGF-C), which promote the proliferation of peripheral lymphatic vessels, on the cerebellar medullary cistern injection of TBI rats, as well as their mechanism of action on brain edema after TBI. In the experiment, we found that ketoprofen, 9-cisRA, and VEGF-C can improve the function of MLVs, promote the extracranial drainage of CSF and the absorption of brain edema, weaken the neuroinflammatory response, reduce reactive oxygen species (ROS) production, maintain the structural integrity of MLVs, and improve neurological function. In addition, ketoprofen, 9-cisRA, and VEGF-C upregulated the lymphatic-specific proteins VEGF receptor (VEGFR)3, PROX1, forkhead box protein C2 (FOXC2), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1). These results indicate that ketoprofen, 9-cisRA, and VEGF-C may maintain the integrity of the meningeal lymphatic wall and promote lymphatic proliferation by upregulating the expression of lymphatic vessel-specific proteins, improve meningeal lymphatic function after TBI, promote CSF drainage and brain edema absorption, reduce the immune response of the nervous system, and reduce ROS formation, thereby improving prognoses. These findings may provide new ideas for the treatment of brain edema after TBI.

Treatment of Anterior Dislocation of the Sacroiliac Joint via the Lateral-rectus Approach: Surgical Techniques and Preliminary Outcomes.

OBJECTIVE: Anterior dislocation of the sacroiliac joint (ADSIJ) is caused by strong violence, and because of its low morbidity, there are no standardized diagnostic and therapeutical guidelines at this moment. This study aims to explore the surgical techniques and preliminary outcomes of the lateral-rectus approach (LRA) for treating ADSIJ. METHODS: A retrospective study was conducted of 15 patients with ADSIJ from January 2016 to January 2021. The patients' age ranged from 1.8 years old to 57 years old (37 ± 18 years old). All patients underwent open reduction and internal fixation (ORIF) through the LRA. Eight patients were combined with lumbosacral plexus injury and underwent neurolysis during operation. Patients' fracture type, mechanism of injury, associated injuries, operation time and intraoperative bleeding volume were accessed by reviewing medical history. Quality of fracture reduction was evaluated with the Matta score. At 1-year follow-up, the functional rehabilitation was evaluated by the Majeed rehabilitation criteria. For those with lumbosacral plexus injury, the neuromotor function was evaluated using muscle strength grading proposed by the British Medical Research Council (BMRC) and recovery was recorded. RESULTS: All 15 patients underwent the operation successfully. The surgical time ranged from 70 to 220 min (126 ± 42 min), and the intraoperative blood loss ranged from 180 to 2000 mL (816 ± 560 mL). Eighty percent of the cohort (12/15) were rated as excellent and good in the Matta score for fracture reduction quality after operation without surgical incision-related complications. At 1-year follow-up, the overall excellent and good rate was 73.3% (11/15) according to the Majeed criteria, the neuromotor function recovered completely in six cases and partially in two cases according to the BMRC muscle strength grading, and the recovery of sensory function was evaluated as excellent in six cases, good in one case and poor in one case, with an overall excellent and good rate of 87.5%. CONCLUSION: The LRA can well expose the surrounding structures of the sacroiliac joint from the front, which helps surgeons reduce and fix the anterior dislocation of the sacroiliac joint under direct vision and effectively decompress the entrapment of the lumbosacral plexus to achieve better clinical efficacy.

The Prognostic Impact of Radiotherapy in Conjunction with Temozolomide in Diffuse Intrinsic Pontine Glioma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Diffuse intrinsic pontine glioma (DIPG) is a rare and devastating brainstem glioma that occurs predominately in children. To date, the prognostic impact of radiotherapy (RT) in conjunction with temozolomide (TMZ) in DIPG has not been thoroughly analyzed. The aim of this meta-analysis was to analyze the effectiveness of RT quantitatively and precisely in conjunction with TMZ in improving the prognosis of DIPG. METHODS: A systematic search of 8 electronic databases was conducted. Articles mainly discussing the prognostic impact of RT in conjunction with TMZ in DIPG were selected. The pooled 1- and 2-year overall survival (OS) and progression-free survival (PFS) were calculated. RESULTS: A total of 14 studies fulfilled our inclusion criteria, involving 283 cases of patients with DIPG who were treated with RT in conjunction with TMZ. The pooled 1- and 2-year OS of this treatment was 43% and 11%, respectively. The pooled 1- and 2-year PFS was 20% and 2%, respectively. Subgroup analysis revealed that the heterogeneity remained almost the same in all stratum. Egger's test demonstrated that the possibility of publication bias was low. CONCLUSIONS: Requirements of up-to-date evidence on evaluating the prognostic impact of this therapy are urgent.

ROS-Eliminating Carboxymethyl Chitosan Hydrogel to Enhance Burn Wound-Healing Efficacy.

Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.

Mesenchymal Stem Cell-Specific and Preosteoblast-Specific Ablation of TSC1 in Mice Lead to Severe and Slight Spinal Dysplasia, Respectively.

BACKGROUND: TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. RESULTS: No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. CONCLUSION: Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs.

Impairment of Bitter Taste Sensor Transient Receptor Potential Channel M5-Mediated Aversion Aggravates High-Salt Intake and Hypertension.

Excessive salt consumption leads to cardiovascular diseases. Despite various measures designed to reduce salt intake, daily salt intake remains at a high level. Appropriate salt intake is balanced by salt taste preference triggered by epithelium sodium channel and salt taste aversion evoked by bitter taste sensor, transient receptor potential channel M5 (TRPM5). However, the behavioral mechanism of excessive salt intake remains largely elusive. In this study, wild type and TRPM5-/- mice were applied to study the influence of high-salt administration on epithelium sodium channel/TRPM5 and the associated behavior to salt consumption. We found that long-term high-salt intake impaired the aversive behavior to high-salt stimulation but did not alter the preference to low salt in mice. The mechanistic evidence demonstrated that high-salt intake blunted the TRPM5-mediated aversive behavior to noxious salt stimulation through inhibiting PKC (protein kinase C) activity and PKC-dependent threonine phosphorylation in the tongue epithelium but did not affect the epithelium sodium channel-dependent salt taste preference. Inhibition of TRPM5 also resulted in an impaired aversive response to high salt, with reduced taste perception in bitter cortical field of mice. TRPM5-/- mice showed a lowered aversion to high-salt diet and developed salt-induced hypertension. The impaired perception to bitter taste evoked by high-salt intake also existed in hypertensive patients with high-salt consumption. We demonstrate that long-term high-salt consumption impairs aversive response to concentrated salt by downregulating bitter taste sensor TRPM5. It suggests that enhancing TRPM5 function might antagonize excessive salt intake and high salt-induced hypertension.