Anti-diabetic drug canagliflozin hinders skeletal muscle regeneration in mice.

Canagliflozin is an antidiabetic medicine that inhibits sodium-glucose cotransporter 2 (SGLT2) in proximal tubules. Recently, it was reported to have several noncanonical effects other than SGLT2 inhibiting. However, the effects of canagliflozin on skeletal muscle regeneration remain largely unexplored. Thus, in vivo muscle contractile properties recovery in mice ischemic lower limbs following gliflozins treatment was evaluated. The C2C12 myoblast differentiation after gliflozins treatment was also assessed in vitro. As a result, both in vivo and in vitro data indicate that canagliflozin impairs intrinsic myogenic regeneration, thus hindering ischemic limb muscle contractile properties, fatigue resistance recovery, and tissue regeneration. Mitochondrial structure and activity are both disrupted by canagliflozin in myoblasts. Single-cell RNA sequencing of ischemic tibialis anterior reveals a decrease in leucyl-tRNA synthetase 2 (LARS2) in muscle stem cells attributable to canagliflozin. Further investigation explicates the noncanonical function of LARS2, which plays pivotal roles in regulating myoblast differentiation and muscle regeneration by affecting mitochondrial structure and activity. Enhanced expression of LARS2 restores the differentiation of canagliflozin-treated myoblasts, and accelerates ischemic skeletal muscle regeneration in canagliflozin-treated mice. Our data suggest that canagliflozin directly impairs ischemic skeletal muscle recovery in mice by downregulating LARS2 expression in muscle stem cells, and that LARS2 may be a promising therapeutic target for injured skeletal muscle regeneration.

Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement.

BACKGROUND: We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50). METHODS: A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 µg/mL. Then, alfentanil 15 µg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection. RESULTS: The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups. CONCLUSION: The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .

Bibliometric analysis and visualization of research trends on oblique lumbar interbody fusion surgery.

PURPOSE: To determine trends and hot subjects in the field of oblique lumbar interbody fusion (OLIF) research during the last decade using bibliometric analysis and visualization tools, in order to assist researchers in exploring new directions for future research in that field. METHODS: Articles published from January 1, 2012, to August 15, 2021, were screened in the Web of Science database. The data were analyzed with CiteSpace software, which generated visualization knowledge maps. All literature was assessed for the following parameters: the number of total publications, distribution, h-index, institutions, journals, authors, co-occurrence state, and research hotspots. RESULTS: A total of 173 articles were identified. The country with the largest number of articles was China (41.04%), followed by South Korea (20.81%), the USA (15.61%), Japan (9.83%), and Thailand (2.89%). South Korea and the USA had the highest h-index (9), followed by China (8), Japan (7), and Thailand (2). Catholic University of Korea was the organization that produced the most literature. World Neurosurgery published the most papers about OLIF (12.50%), but articles in Spine were most frequently cited (151). Kim JS was the most productive author, whereas Silvestre C was the most cited author. The main research hotspots are anatomy, discectomy, approach, injure, and diseases. CONCLUSIONS: The number of publications in the field of OLIF has increased considerably in recent years. The USA, China, South Korea, and Japan have made substantial contributions to this field. Anatomy, complications, decompression surgery, and application in various degenerative lumbar diseases have been the research hotspots in recent years.

Maize transcription factor ZmNF-YC13 regulates plant architecture.

Leaf angle and leaf orientation value (LOV) are critical agronomic traits for maize plant architecture. The functions of NUCLEAR FACTOR Y (NF-Y) members in regulating plant architecture have not been reported yet. Here, we identified a regulator of maize plant architecture, NF-Y subunit C13 (ZmNF-YC13). ZmNF-YC13 was highly expressed in the leaf base zone of maize plants. ZmNF-YC13 overexpressing plants showed upright leaves with narrow leaf angle and larger LOV, while ZmNF-YC13 knockout plants had larger leaf angle and smaller LOV compared with wild-type plants. The changes in plant architecture were due to the changes in the expression of cytochrome P450 family members. ZmNF-YC13 interacts with two NF-Y subunit B members (ZmNF-YB9 and ZmNF-YB10) of the LEAFY COTYLEDON1 sub-family, and further recruits NF-Y subunit A (ZmNF-YA3) to form two NF-Y complexes. The two complexes can both activate the promoters of transcriptional repressors (ZmWRKY76 and ZmBT2), and the promoters of PLASTOCHRON group genes can be repressed by ZmWRKY76 and ZmBT2 in maize protoplasts. We propose that ZmNF-YC13 functions as a transcriptional regulator and, together with ZmNF-YBs and ZmNF-YA3, affects plant architecture by regulating the expression of ZmWRKY76 and ZmBT2, which repress the expression of cytochrome P450 family members in PLASTOCHRON branch.

Discovery of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors.

Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50 values of 0.004 µM and 0.001 µM against ROCK Ⅰ and ROCK Ⅱ, respectively. In vitro, 8k significantly reduced the phosphorylation level of ROCK downstream signaling protein and induce changes in cell morphology and migration. Overall, this study provides a promising lead compound for drug discovery targeting ROCKs.

Knockdown of ELMO3 Suppresses Growth, Invasion and Metastasis of Colorectal Cancer.

The engulfment and cell motility (ELMOs) family of proteins plays a crucial role in tumor cell migration and invasion. However, the function of ELMO3 is poorly defined. To elucidate its role in the development and progression of colorectal cancer (CRC), we examined the expression of ELMO3 in 45 cases of paired CRC tumor tissues and adjacent normal tissues. Furthermore, we assessed the effect of the knockdown of ELMO3 on cell proliferation, cell cycle, migration, invasion and F-actin polymerization in HCT116 cells. The result shows that the expression of ELMO3 in CRC tissues was significantly increased in comparison to the adjacent normal colorectal tissues. Moreover, this overexpression was associated with tumor size (p = 0.007), tumor differentiation (p = 0.001), depth of invasion (p = 0.009), lymph node metastasis (p = 0.003), distant metastasis (p = 0.013) and tumor, node, metastasis (TNM)-based classification (p = 0.000). In in vitro experiments, the silencing of ELMO3 inhibited cell proliferation, invasion, metastasis, and F-actin polymerization, and induced Gap 1 (G1) phase cell cycle arrest. Our study demonstrates that ELMO3 is involved in the processes of growth, invasion and metastasis of CRC, and could be used a potential molecular diagnostic tool or therapy target of CRC.

Reverse sequential therapy achieves a similar eradication rate as standard sequential therapy for Helicobacter pylori eradication: a randomized controlled trial.

BACKGROUND AND AIMS: Sequential therapy is a two-step therapy achieving a promising eradication rate for Helicobacter pylori infection. The rationale of sequential method has been proposed that amoxicillin weakens bacterial cell walls in the initial phase of treatment, preventing the development of drug efflux channels for clarithromycin and metronidazole used in the second phase. The aim of this prospective, randomized, controlled study was to investigate whether the efficacy of reverse sequential therapy was noninferior to sequential therapy in the treatment of H. pylori infection. METHODS: From January 2009 to December 2010, consecutive H. pylori-infected patients were randomly assigned to receive either sequential therapy (a 5-day dual therapy with pantoprazole plus amoxicillin, followed by a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole) or reverse sequential therapy (a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole, followed by a 5-day dual therapy with pantoprazole plus amoxicillin). H. pylori status was examined 6 weeks after the end of treatment by rapid urease and histology or urea breath test. RESULTS: One hundred and twenty-two H. pylori-infected participants were randomized to receive sequential (n = 60) or reverse sequential therapy (n = 62). The eradication rates, by intention-to-treat analysis, were similar: 91.9% (95% confidence interval (CI): 85.1-98.7%) for sequential therapy and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .44). Per-protocol analysis also showed similar results: 91.8% (95% CI: 84.9-98.7%) for sequential group and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .43). The two treatments exhibited comparable frequencies of adverse events (11.3% vs 6.7%, respectively) and drug compliance (98.4% vs 100%, respectively). The overall resistance rates of antibiotics were clarithromycin 10.5%, amoxicillin 0%, and metronidazole 44.2% of patients, respectively. The dual resistance rate of clarithromycin and metronidazole was 4.2%. Both therapies achieved a high eradication rate for clarithromycin-resistant strains (100% vs 100%, respectively) and metronidazole-resistant strains (81.8% vs 95%, respectively) by intention-to-treat analysis. CONCLUSIONS: Ten-day reverse sequential therapy and standard sequential therapy are equally effective for H. Pylori eradication. The finding indicates that the sequence of antibiotics administered in sequential therapy does not influence the efficacy of the treatment.

A Temperature Prediction Model for Flexible Electronic Devices Based on GA-BP Neural Network and Experimental Verification.

The problem that the thermal safety of flexible electronic devices is difficult to evaluate in real time is addressed in this study by establishing a BP neural network (GA-BPNN) temperature prediction model based on genetic algorithm optimisation. The model uses a BP neural network to fit the functional relationship between the input condition and the steady-state temperature of the equipment and uses a genetic algorithm to optimise the parameter initialisation problem of the BP neural network. To overcome the challenge of the high cost of obtaining experimental data, finite element analysis software is used to simulate the temperature results of the equipment under different working conditions. The prediction variance of the GA-BPNN model does not exceed 0.57 °C and has good robustness, as the model is trained according to the simulation data. The study conducted thermal validation experiments on the temperature prediction model for this flexible electronic device. The device reached steady state after 1200 s of operation at rated power. The error between the predicted and experimental results was less than 0.9 °C, verifying the validity of the model's predictions. Compared with traditional thermal simulation and experimental methods, this model can quickly predict the temperature with a certain accuracy and has outstanding advantages in computational efficiency and integrated application of hardware and software.

Intelligent wearable olfactory interface for latency-free mixed reality and fast olfactory enhancement.

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.

Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. METHODS: A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. RESULTS: The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. CONCLUSION: Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.

Skin-Integrated Wireless Odor Message Delivery Electronics for the Deaf-blind.

Deaf-blindness limits daily human activities, especially interactive modes of audio and visual perception. Although the developed standards have been verified as alternative communication methods, they are uncommon to the nondisabled due to the complicated learning process and inefficiency in terms of communicating distance and throughput. Therefore, the development of communication techniques employing innate sensory abilities including olfaction related to the cerebral limbic system processing emotions, memories, and recognition has been suggested for reducing the training level and increasing communication efficiency. Here, a skin-integrated and wireless olfactory interface system exploiting arrays of miniaturized odor generators (OGs) based on melting/solidifying odorous wax to release smell is introduced for establishing an advanced communication system between deaf-blind and non-deaf-blind. By optimizing the structure design of the OGs, each OG device is as small as 0.24 cm3 (length × width × height of 11 mm × 10 mm × 2.2 mm), enabling integration of up to 8 OGs on the epidermis between nose and lip for direct and rapid olfactory drive with a weight of only 24.56 g. By generating single or mixed odors, different linked messages could be delivered to a user within a short period in a wireless and programmable way. By adopting the olfactory interface message delivery system, the recognition rates for the messages have been improved 1.5 times that of the touch-based method, while the response times were immensely decreased 4 times. Thus, the presented wearable olfactory interface system exhibits great potential as an alternative message delivery method for the deaf-blind.

Thermal Management of Serpentine Flexible Heater Based on the Orthotropic Heat Conduction Model.

Flexible heaters can perfectly fit with undevelopable surfaces for heating in many practical applications such as thermotherapy, defogging/deicing systems and warming garments. Considering the requirement for stretchability in a flexible heater, certain spacing needs to be retained between serpentine heat sources for deformation which will inevitably bring critical challenges to the thermal uniformity. In order to reconcile these two conflicting aspects, a novel method is proposed by embedding the serpentine heat source in orthotropic layers to achieve comprehensive performance in stretchability and uniform heating. Such a scheme takes advantage of the ability of orthotropic material to control the heat flow distribution via orthotropic thermal conductivity. In this paper, an analytical heat conduction model with orthotropic substrate and encapsulation is calculated using Fourier cosine transform, which is validated by finite element analysis (FEA). Meanwhile, the effects of the orthotropic substrate or encapsulation with different ratios of thermal conductivity and the geometric spacing on the thermal properties are investigated, which can help guide the design and fabrication of flexible heaters to achieve the goal of uniform heating.

Supratentorial hemangioblastoma at the anterior skull base: A case report.

BACKGROUND: Hemangioblastoma (HB) is a rare tumor, comprising about 2% of all intracranial tumors. Although it is a benign tumor, due to the abundant blood supply and its close relationship with adjacent cerebral blood vessels, surgical resection is difficult and may cause complications such as bleeding. If HB can be correctly diagnosed before surgery, complications can be avoided by methods such as vascular embolism before surgery. CASE SUMMARY: A 51-year-old male patient was admitted to our hospital because of blurred vision in his left eye for 2 years. Ophthalmological examination revealed oculus dexter vision acuity of 1.0 and oculus sinister vision acuity of 0.6. His left vision had tubular visual field, while his right vision had a partial defect. Computed tomography and magnetic resonance imaging showed a mass lesion at the left anterior base of the skull, which could have been a meningioma. During the operation, the tumor was found to be located at the entrance of the left optic nerve tube, closely adhering to the left optic nerve and the blood supply was extremely abundant. The tumor was carefully separated and diagnosed as HB postoperatively after pathological examination. CONCLUSION: A rare HB at the anterior skull base could be distinguished by its imaging features, which is essential to the surgical procedures.

An Analytic Orthotropic Heat Conduction Model for the Stretchable Network Heaters.

Compared with other physiotherapy devices, epidermal electronic systems (EES) used in medical applications such as hyperthermia have obvious advantages of conformal attachment, lightness and high efficiency. The stretchable flexible electrode is an indispensable component. The structurally designed flexible inorganic stretchable electrode has the advantage of stable electrical properties under tensile deformation and has received enough attention. However, the space between the patterned electrodes introduced to ensure the tensile properties will inevitably lead to the uneven temperature distribution of the thermotherapy electrodes and degrade the effect of thermotherapy. It is of great practical value to study the temperature uniformity of the stretchable patterned electrode. In order to improve the uniformity of temperature distribution in the heat transfer system with stretchable electrodes, a temperature distribution manipulation strategy for orthotropic substrates is proposed in this paper. A theoretical model of the orthotropic heat transfer system based on the horseshoe-shaped mesh electrode is established. Combined with finite element analysis, the effect of the orthotropic substrate on the uniformity of temperature distribution in three types of heat source heat transfer systems is studied based on this model. The influence of the thermal conductivity ratio in different directions on the temperature distribution is studied parametrically, which will help to guide the design and fabrication of the stretchable electrode that can produce a uniform temperature distribution.

Somatosensory rub evoked reflex epilepsy of a temporal lobe origin.

Somatosensory rub reflex epilepsy, evoked by prolonged or repetitive cutaneous contact of a circumscribed body area, is an unusual form of reflex epilepsy. The peculiar complaints and the negative interictal electroencephalographic (EEG) recordings make it difficult to identify the epileptic origin. Here we report an unusual case whose seizures would be evoked by a touch or rub on a unilateral arm and shoulder, with a contralateral temporal lobe origin, demonstrated in immediate postictal single-photon emission computed tomography (SPECT).

Influencing Mechanism of Justice Sensitivity on Knowledge Hiding in the Chinese Context.

Good knowledge management is important for enterprises to maintain competitive advantage; however, the knowledge hiding behavior may hinder this process. Based on the conservation of resources and psychological ownership theories, using a chain intermediary model, this study investigates the effect of justice sensitivity on knowledge hiding through perceived time pressure and territoriality, and further tests the moderating role of territoriality. For the study, we collected 436 questionnaires from China through the Wenjuanxing Sample Service, of which 391 were valid. We then conducted multiple regression analysis and employed the bootstrap method for our tests. The results show that victim sensitivity has a significant effect on perceived time pressure, territoriality, and knowledge hiding, and that a chain mediating effect of perceived time pressure and territoriality is established between justice sensitivity and knowledge hiding. Further, territoriality has a positive moderating effect on perceived time pressure and knowledge hiding, while the mediating effect of perceived time pressure on justice sensitivity and knowledge hiding is also moderated by territoriality. Further, the study offers important practical implications in that enterprises should not blindly pursue results by making employees work excessively overtime. And there should have rationalized regulations in organization to ensure justice. The management should pay close attention to the psychological problems of victim and perpetrator. Instead, enterprises should have a certain degree of control, offer rationales for overtime work, and give high wages to the employees to compensate for their time, thus making the employees feel the worthiness of their overtime work and reducing the probability of engaging in knowledge hiding behaviors.

18F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus.

PURPOSE: Hepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT. METHODS: Five hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT. RESULTS: Our results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS. CONCLUSION: SUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.

ß-Catenin expression is associated with cell invasiveness in pancreatic cancer.

BACKGROUND/AIMS: This study was tried to determine the role of ß-catenin in invasion in pancreatic cancer. METHODS: We analyzed cancer invasiveness according to ß-catenin expression in pancreatic cancer cell line. We also investigated the change in cancer invasiveness when ß-catenin expression was changed. To enhance ß-catenin activity, we treated low ß-catenin cancer cell line, PANC1, with Wnt-3a conditioned media and transected ß-catenin. We also treated high ß-catenin expressing cell line, BxPC3, with XAV939, ß-catenin inhibitor and siRNA for ß-catenin to inhibit ß-catenin expression. RESULTS: The high ß-catenin expressing cancer cell line, BxPC3 showed higher invasiveness, and low ß-catenin expressing cell lines, PANC1and MIA-PaCa-2, were less invasive. By adding the Wnt-3a conditioned media or performing transfection with ß-catenin in PANC1, cell invasiveness was increased (p < 0.05 and p < 0.01, respectively). On inhibition of ß-catenin by XAV939 and siRNA in BxPC3 cell line, invasiveness was significantly decreased (p < 0.01). It was not correlated with the expression of cluster of differentiation 44 (CD44) or CD44 variant 6 (CD44v6), the invasion related protein. On analysis of association with metastasis in human tissue, Wnt-3a expression was statistically correlated with the development of metastasis (p = 0.029). CONCLUSION: Based on our data, ß-catenin may be involved in cancer invasion in pancreatic cancer, and it is not associated with CD44, the invasion related protein.