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Spinal cord injury (SCI) is a devastating disease with limited treatment options due to the restricted regenerative capacity of the central nervous system. The accumulation of reactive oxygen species (ROS) and inadequate endogenous neural stem progenitor cells (eNSPCs) in the lesion site exacerbates neurologic deficits and impedes motor function recovery. We have developed a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel. Microglia cells treated with PDA NPs have been shown to reduce intracellular ROS levels by 65 % and suppress the expression of inflammatory cytokines such as IL-1β (decreased by 35 %) and IL-6 (decreased by 23 %), thus mitigating the microglia's inflammatory response. Additionally, our results have demonstrated that the H-P-M hydrogel combined with hMSCs transplantation can recruit eNSPCs to the injury site as evidenced by utilizing Nestin lineage tracer mice. The RNA-seq has unveiled the potential of the H-P-M hydrogel to facilitate eNSPCs neuronal differentiation through the MAPK pathway. Furthermore, these differentiated neurons are integrated into local neural circuits. Together, it suggests that the H-P-M hydrogel synergistically improves the SCI niche. It serves as catalysts inducing 5-HT axon regeneration and improving BMS score after SCI through the modulation of the ROS milieu and the promotion of neuronal differentiation from eNSPCs, thereby presenting a promising strategy for SCI repair.

The transport and transfer of radionuclides in the ecological environment (referred to migration) have long been of a particular concern in the field of radiological environmental protection. This paper systematically reviews the current relevant research statuses on mechanisms, models and parameters of radionuclide migration in the ecological environment, and the methods for assessing doses of humans and non-human species, as well as the non-equilibrium migration models and parameters of radionuclide migration in case of accident at a nuclear facility. From multi-dimensional perspectives, such as computational models, evaluation methods, and parameters, etc., this paper explores the transport and transfer behaviors of radionuclides in the ecological environment. In terms of radionuclide migration, this paper systematically reviews the transport processes and migration models of radionuclides from source term release to atmospheric, terrestrial, surface water (rivers, lakes, etc.), groundwater, and marine environments. It elaborates on the basic theories of radionuclide transport and transfer in the ecological environment, compares the characteristics of different transport modes, and summarizes the transport and transfer behaviors of radionuclides in the ecological environment. In terms of environmental radiation exposure assessment, this paper summarizes both individual-related and source-related evaluation methods, describing the basic methods of environmental radiation exposure assessment. It presents a schematic diagram of the main steps and dose estimation models for assessing the impact of radionuclides released into the environment, and sorts out the methods, evaluation models, and dose assessment software for exposure assessment from the perspectives of both the human and non-human species, domestically and internationally. Moreover, for environmental radiation exposure assessment in case of accidents, this paper takes tritium and 14C as examples to provide an overview of short-term migration, accident exposure assessment, and real-time consequence evaluation and decision support for nuclear accidents. It proposes suggestions for further research in the aspects of radionuclide marine transport, dose assessment models for non-human species, short-term accidental release, and the application of artificial intelligence, to provide scientific basis and technical support for nuclear and radiation emergency response, environmental monitoring, and risk assessment.

To improve the electrocatalytic transformation of carbon dioxide (CO2) to multi-carbon (C2+) products is of great importance. Here we developed a nitrogen-doped Cu catalyst, by which the maximum C2+ Faradaic efficiency can reach 72.7% in flow-cell system, with the partial current density reaching 0.62 A cm−2. The in situ Raman spectra demonstrate that the ∗CO adsorption can be strengthened on such a N-doped Cu catalyst, thus promoting the ∗CO utilization in the subsequent C–C coupling step. Simultaneously, the water activation can be well enhanced by N doping on Cu catalyst. Owing to the synergistic effects, the selectivity and activity for C2+ products over the N-deoped Cu catalyst are much improved.

Abstract Bladder cancer (BLCA) is a prevalent cancer with high case‐fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non‐apoptotic form of cell death, is initiated by the lethal accumulation of iron‐dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re‐analysis of single‐cell RNA data reveals a decrease in high‐ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT protein degradation, increasing lipid peroxidation and ferroptosis susceptibility, thus suppressing BLCA progression. Mechanistically, USP52 interacts with xCT and enzymatically cleaves the K48‐conjugated ubiquitin chains at K4 and K12, enhancing its protein stability. Clinical BLCA samples demonstrate a positive correlation between USP52 and xCT expression, with high USP52 levels associated with aggressive disease progression and poor prognosis. In vivo, USP52 depletion combined with ferroptosis triggers imidazole ketone Erastin (IKE) synergistically restrains BLCA progression by inducing ferroptosis. These findings elucidate the role of the USP52‐xCT axis in BLCA and highlight the therapeutic potential of targeting USP52 and ferroptosis inducers in BLCA.

Background: Ginsenosides (GS), including total GS, Rh2, Rg3 and compound K (CK), have been utilized as adjuvants in transarterial chemoembolization (TACE), surgery, and chemotherapy for hepatocellular carcinoma (HCC) therapy. However, the safety and efficacy of such combination treatments have been contradictory across different studies. This study aims to systematically evaluate the efficacy and safety of GS as adjuvant therapy for HCC. Methods : A literature search of PubMed, CNKI, Wanfang Data, Cochrane Library, Embase, and Web of Science was conducted up to May 2024 for clinical randomized controlled trials (RCTs) on GS-based adjuvant treatments for HCC. Two researchers independently screened the literature, extracted relevant data, and assessed study quality. Meta-analysis was conducted using RevMan 5.4. Results : Nineteen articles involving 1448 patients were included. Meta-analysis showed that GS as an adjuvant therapy for HCC improved disease control rate (risk ratio (RR) = 1.42, 95% CI [1.26, 1.60]), objective response rate (RR = 1.20, 95% CI [1.09, 1.32]), life quality (RR = 1.49, 95% CI [1.23, 1.79]), 1-year overall survival rate (RR = 1.27, 95% CI [1.06, 1.52]), 2-year overall survival rate (RR = 1.43, 95% CI [1.06, 1.95]), ehanced Child-Pugh in A level (RR = 1.59, 95% CI [1.08, 2.34]), Child-Pugh in B level (RR = 1.28, 95% CI [1.08, 1.52]); increased CD3 + (MD = 8.81, 95% CI [3.91, 13.71]), NKC (MD = 8.00, 95% CI [6.76, 9.24]) and CD4 + (MD = 9.38, 95% CI [8.04, 10.72]), and reduced incidence of adverse reactions including nausea and vomiting (RR = 0.66, 95% CI [0.57, 0.77]), anorexia (RR = 0.33, 95% CI [0.21, 0.50]), leukopenia (RR = 0.55, 95% CI [0.46, 0.67]) and myelosuppression (RR = 0.54, 95% CI [0.40, 0.74]); decreased Child-Pugh in C level (RR = 0.43, 95% CI [0.27, 0.68]) and CD4 + /CD8 + ratio (MD = 0.50, 95% CI [0.47, 0.57]). Conclusions : In summary, GS combined with Western medical approaches (TACE, surgery, chemotherapy) for the treatment of HCC can improve clinical efficacy, increase overall survival rates, enhance patient life quality, and reduce the occurrence of adverse reactions. However, due to the generally low quality of the included studies, more large-sample, multi-center, high-quality, RCTs are warranted to further consolidate these findings.

At present, wireless power transfer (WPT) systems with constant current (CC) or constant voltage (CV) characteristics are typically achieved using a single transmitter and single pickup (STSP) configuration, which cannot transfer power to multiple battery loads simultaneously. In this paper, the LCC-LCC/S reconfigurable topology is proposed to realize the CC-to-CV transition for multiple battery loads. An LCC topology is designed on the primary side to achieve a constant current (0.362A) flowing through the transmitting coil to enable independent operation of power pickups. A reconfigurable LCC/S topology is designed on the secondary side to achieve the CC-to-CV transition of the battery loads. The received power from the pickups remains unaffected when pickups are moved in or out or are in different operating modes (CC or CV). The circuit can maintain zero phase angle (ZPA) operation, which greatly enhances the overall power density of the system. Additionally, detailed design process for the compensation parameters on both the primary and secondary sides are provided. Theoretical analysis proves that good system stability and robustness can be obtained in the case of variable quantity of pickups and quality factors of coils. The experimental prototype was built, with the CC value for the battery load designed at 0.7A and the CV value designed at 8 V. Experimental results demonstrate the smooth CC-to-CV transition of the proposed WPT system (with 3 pickups) at a power output of 15.4 W, and the system’s maximum efficiency can reach 75.5 %.

BackgroundThis study aims to explore the analgesic effect of lidocaine administered through the hepatic artery during hepatic artery infusion chemotherapy (HAIC) for hepatocellular carcinoma (HCC).MethodsA total of 45 HCC patients were randomly divided into a study group and a control group. Both groups received oxaliplatin (OXA) based FOLFOX protocol via electronic infusion pump. The study group was continuously infused with 100 mg of lidocaine during HAIC, while 5% glucose solution was infused in the same way as described above. Changes in vital signs, visual analogue score (VAS) and general comfort score (GCQ scale) were recorded before surgery (Time point 0), at the end of infusion (Time point 01), 1 h after HAIC (Time point 02), 3 h after HAIC (Time point 03) and 6 h after HAIC (Time point 04).ResultsAt each point of time from Time point 0 through Time point 04, the differences in MAP, RR and SPO2 between the two groups were not statistically significant (P > 0.05). At each point of time from Time point 01 through Time point 04, the mean VAS scores in the study group were smaller and GCQ scores were higher than those in the control group, and the differences were both statistically significant (P

Abstract PRKN is a key gene involved in mitophagy in Parkinson’s disease. However, recent studies have demonstrated that it also plays a role in the development and metastasis of several types of cancers, both in a mitophagy-dependent and mitophagy-independent manner. Despite this, the potential effects and underlying mechanisms of Parkin on bladder cancer (BLCA) remain unknown. Therefore, in this study, we investigated the expression of Parkin in various BLCA cohorts derived from human. Here we show that PRKN expression was low and that PRKN acts as a tumor suppressor by inhibiting the proliferation and migration of BLCA cells in a mitophagy-independent manner. We further identified Catalase as a binding partner and substrate of Parkin, which is an important antioxidant enzyme that regulates intracellular ROS levels during cancer progression. Our data showed that knockdown of CAT led to increased intracellular ROS levels, which suppressed cell proliferation and migration. Conversely, upregulation of Catalase decreased intracellular ROS levels, promoting cell growth and migration. Importantly, we found that Parkin upregulation partially restored these effects. Moreover, we discovered that USP30, a known Parkin substrate, could deubiquitinate and stabilize Catalase. Overall, our study reveals a novel function of Parkin and identifies a potential therapeutic target in BLCA.

Abstract A hallmark of tumor cells, including bladder cancer (BLCA) cells, is metabolic reprogramming toward aerobic glycolysis (Warburg effect). The classical oncogene MYC, which is crucial in regulating glycolysis, is amplified and activated in BLCA. However, direct targeting of the c-Myc oncoprotein, which regulates glycolytic metabolism, presents great challenges and necessitates the discovery of a more clarified regulatory mechanism to develop selective targeted therapy. In this study, a siRNA library targeting deubiquitinases identified a candidate enzyme named USP43, which may regulate glycolytic metabolism and c-Myc transcriptional activity. Further investigation using functional assays and molecular studies revealed a USP43/c-Myc positive feedback loop that contributes to the progression of BLCA. Moreover, USP43 stabilizes c-Myc by deubiquitinating c-Myc at K148 and K289 primarily through deubiquitinase activity. Additionally, upregulation of USP43 protein in BLCA increased the chance of interaction with c-Myc and interfered with FBXW7 access and degradation of c-Myc. These findings suggest that USP43 is a potential therapeutic target for indirectly targeting glycolytic metabolism and the c-Myc oncoprotein consequently enhancing the efficacy of bladder cancer treatment.

The production of Chi-aroma Baijiu generates free radicals, which may pose potential health risks. This study aimed to scavenge free radicals in Chi-aroma Baijiu and assess the impact on the composition of volatile compounds (VOCs) by using distillers’ grains-derived homologous peptides. Five peptides—Pro-Ala (PA), Pro-Val (PV), Gly-Leu (GL), Asp-Phe (DF), and Pro-Leu (PL)—were isolated from the distillers’ grain filtrate. These peptides are present in trace amounts in Chi-aroma Baijiu. By supplementing five peptides to Chi-aroma Baijiu, they could completely scavenge hydroxyl radicals. The rate of scavenging alkoxy radicals ranged from 10.84% to 35.66%. Furthermore, these peptides had an impact on ethyl nonanoate, diethyl acetal, and octanal, which were recognized as characteristic compounds. Ultraviolet spectroscopy simulation revealed that the highest absorption peaks of certain peptides shift when they interact with various esters. Those peptides interact with ethyl acetate and ethyl lactate via hydrogen bonding and Van der Waals forces, demonstrating their influence on VOCs. These findings offer new insights into free radical scavenging, flavor compound regulation, and the valorization of Baijiu by-products in Chi-aroma Baijiu production.

Objective This study assessed biomechanical properties of pedicle screws enhanced or revised with 3 materials. We aimed to compare the efficacy of these materials in pedicle augmentation and revision. Methods One hundred twenty human cadaveric vertebrae were utilized for in vitro testing. Vertebrae bone density was evaluated. Allograft bone particles (ABP), calcium phosphate cement (CPC), and demineralized bone matrix (DBM) were used to augment or revise pedicle screw. Post the implantation of pedicle screws, parameters such as insertional torque, pullout strength, cycles to failure and failure load were measured using specialized instruments. Results ABP, CPC, and DBM significantly enhanced biomechanical properties of the screws. CPC augmentation showed superior properties compared to ABP or DBM. ABP-augmented screws had higher cycles to failure and failure loads than DBM-augmented screws, with no difference in pullout strength. CPC-revised screws exhibited similar strength to the original screws, while ABP-revised screws showed comparable cycles to failure and failure loads but lower pullout strength. DBM-revised screws did not match the original screws’ strength. Conclusion ABP, CPC, and DBM effectively improve pedicle screw stability for pedicle augmentation. CPC demonstrated the highest efficacy, followed by ABP, while DBM was less effective. For pedicle revision, CPC is recommended as the primary choice, with ABP as an alternative. However, using DBM for pedicle revision is not recommended.

Abstract Objective The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) survivors is concerning. The goal of this study was to investigate and demonstrate the relationship between the neutrophil-to-albumin ratio (NAR) and long-term mortality of aSAH survivors. Methods A retrospective observational cohort study was conducted at Sichuan University West China Hospital between January 2009 and June 2019. The investigation of relationship between NAR and long-term mortality was conducted using univariable and multivariable Cox regression models. To demonstrate the predictive performance of different biomarkers over time, time-dependent receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were created. Results In total, 3173 aSAH patients were included in this study. There was a strong and continuous relationship between NAR levels and long-term mortality (HR 3.23 95% CI 2.75–3.79, p 0.28: adjusted HR 1.74 95% CI 1.30–2.32). Results in survivors were found to be still robust. Moreover, out of all the inflammatory markers studied, NAR demonstrated the highest correlation with long-term mortality. Conclusions A high level of NAR was associated with increased long-term mortality among patients with aSAH. NAR was a promising inflammatory marker for long-term mortality of aSAH.

Abstract To explore the strain rate effect of deformation and failure of impact prone coal rock, uniaxial compression tests and triaxial compression tests with different strain rates were carried out. The mechanical properties and impact tendency of impact-prone coal rock were studied, and the energy evolution law and pre-peak energy self-promotion-inhibition mechanism of impact-prone coal rock were obtained. The results show that with the increase of strain rate, the peak strength of coal rock under uniaxial compression decreases gradually, and the peak strength of coal rock under triaxial compression increases first and then decreases, and the impact tendency of coal rock increases first and then decreases. The energy evolution of coal rock under uniaxial compression is mainly divided into four stages: initial energy damage, energy hardening, energy softening and failure. With the increase of strain rate, the total energy and elasticity at the peak point of coal rock under uniaxial compression decrease gradually, and the total energy, elastic energy and dissipation energy at the peak point under triaxial compression increase first and then decrease. The elastic energy promotion coefficient of impact-prone coal rock is much larger than the inhibition coefficient, and the increase of strain rate will promote the generation of elastic energy inside coal rock. The research results can provide reference for the prevention and early warning of dynamic disasters of coal and rock mass with impact tendency.

Spinal cord injury (SCI) causes motor, sensory and automatic impairment due to rarely axon regeneration. Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury, as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier. To develop an effective non-invasive treatment strategy for SCI in clinic, we generated an autologous plasma exosome (AP-EXO) based biological scaffold where AP-EXO was loaded with neuron targeting peptide (RVG) and growth-facilitating peptides (ILP and ISP). This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment, thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice. More importantly, in ex vivo, human plasma exosomes (HP-EXO) loaded with combinatory peptides of RVG, ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice. Combining the efficacy and safety, the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI. It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.

Abstract This paper proposes a novel cubic WPT system for an enclosed sensor scenario, and its transmission characteristics in a metal environment have been analyzed. In addition, stable and high transmission efficiency can be normally achieved in all positions. The proposed quasi‐double D coil structure is composed of two pairs of transmitting coils; each transmitting coil pair is placed face to face and connected serially. Through current amplitude modulation, magnetic flux can flow towards the centre of the receiving coil and keep the system high efficiency when the rotation angle of the receiving coil changes. However, the installation position of the receiving coil is not fixed in the switch cabinet application, and an irregular iron wall and the metal shell of sensors could also lead to inconsistent iron loss of multiple transmitters. To overcome the resulting disturbances in efficiency, the improved current amplitude control method and the optimal load have been theoretically deduced in the case of the position variation of the receiving coil in a metal environment. Finally, experimental results in two‐dimensional space verify the omnidirectional transmission capability of the proposed quasi‐double D coil, and efficiency disturbances are effectively alleviated.

Spatially Offset Raman Spectroscopy (SORS) has extensively been studied as a non-invasive technique that can detect the internal composition below the surface of turbid samples. A critical application of SORS is to identify unknown materials behind a highly scattering obstacle, such as plastic containers. The mechanism of SORS can be generally demonstrated as the photon migration theory; the Raman photons inside deeper samples are more likely to propagate laterally. However, a comprehensive view of the SORS mechanism still needs to be improved. In this work, a numerical simulation was carried out by the Monte Carlo algorithm to investigate the characteristics of SORS being affected by the various optical properties of materials, such as scattering coefficients, absorption coefficients, and refractive index. The key characteristics of SORS, such as detection depth, optimal offset, and signal intensity, were systematically analyzed in a monolayer medium and a bilayer medium. These findings provide important additional information on SORS theory and have important implications for the development of SORS as a reliable analytical tool in various fields, including biomedical research and environmental monitoring.

BackgroundSmoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients.MethodsThis study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint.ResultsOf the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p

Abstract Ionic liquids (ILs) attract more and more interests in improving drug transport across membrane, including transdermal, nasal, and oral delivery. However, some drawbacks of ILs impede the application in oral drug delivery, such as rapid precipitation of poorly soluble drugs in stomach. This study aimed to employ enteric mesoporous silica nanoparticles (MSNs) to load ILs to overcome the shortcomings faced in oral administration. The choline sorbate ILs (SCILs) were synthesized by choline bicarbonate and sorbic acid and then adsorbed in mesopores of MSNs after dissolving cyclosporin A (CyA). MSNs loading SCILs and CyA were coated by Eudragit® L100 to form enteric nanoparticles. The in vitro release study showed that the CyA and SCILs released only 10% for 2 h in simulated gastric fluids but more than 90% in simulated intestinal fluid. In addition, SCILs and CyA were able to release from MSNs synchronously. After oral administration, enteric MSNs loading SCILs were capable of improving oral absorption of CyA significantly and the oral bioavailability of CyA was similar with that of oral Neoral®. In addition, the oral absorption of enteric MSNs was higher than that of nonenteric MSNs, which showed that enteric coating was necessary to ILs in oral delivery. These findings revealed great potential of translation of ILs to be enteric nanoparticles for facilitating oral absorption of CyA. It is predictable this delivery system is promising to be a platform for delivering poorly water‐soluble drugs and even biologics orally.

ObjectiveMany peripheral inflammatory markers were reported to be associated with the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to identify the most promising inflammatory factor that can improve existing predictive models.MethodsThe study was based on data from a 10 year retrospective cohort study at Sichuan University West China Hospital. We selected the well-known SAFIRE and Subarachnoid Hemorrhage International Trialists’ (SAHIT) models as the basic models. We compared the performance of the models after including the inflammatory markers and that of the original models. The developed models were internally and temporally validated.ResultsA total of 3,173 patients were included in this study, divided into the derivation cohort (n = 2,525) and the validation cohort (n = 648). Most inflammatory markers could improve the SAH model for mortality prediction in patients with aSAH, and the neutrophil-to-albumin ratio (NAR) performed best among all the included inflammatory markers. By incorporating NAR, the modified SAFIRE and SAHIT models improved the area under the receiver operator characteristics curve (SAFIRE+NAR vs. SAFIRE: 0.794 vs. 0.778, p = 0.012; SAHIT+NAR vs. SAHIT: 0.831 vs. 0.819, p = 0.016) and categorical net reclassification improvement (SAFIRE+NAR: 0.0727, p = 0.002; SAHIT+NAR: 0.0810, p

The transplantation of GABAergic neuron cells has been reported to alleviate nerve pain and improve motor function after spinal cord injury (SCI). However, human mesenchymal stem cell (hMSC) differentiation into GABAergic neuron cells in a sufficient quantity remains to be accomplished. From a database screening, cAMP-responsive element-binding protein 1 (CREB1) was chosen as a potential modulator due to its critical role in the protein–protein interaction of genes related to GABAergic neural differentiation. Here, CREB1 was overexpressed in transfected hMSCs, where CREB1 could induce differentiation into GABAergic neuron cells with an upregulation of Map2 and GAD1 by 2- and 3.4-fold, respectively. Additionally, GABAergic neural differentiation was enhanced, while Notch signaling was inhibited, and BRN2 transcriptional activation played an important role in neuronal maturation. Moreover, transfected hMSCs injected into immunocompromised mice caused by CsA exhibited the neuronal markers Tuj1 and Map2 via the intraspinal route, suggesting an improvement in survival and neural differentiation. Significantly, improvement in both BMS scores (6.2 ± 1.30 vs. 4 ± 0) and thermal hyperalgesia latency (7.74 ± 2.36 s vs. 4.52 ± 0.39 s) was seen compared with the SCI naïve treatment at 4 weeks post-transplantation. Our study demonstrates that CREB1 is crucial in generating induced GABAergic neuron cells (iGNs) originating from hMSCs. Transplanting iGNs to injured spinal cord provides a promising strategy for alleviating neuropathic pain and locomotion recovery after SCI.

Peroxisomes are single-membrane-bound organelles that play critical roles in eukaryotic cellular functions. Peroxisome quantity is a key factor influencing the homeostasis and pathogenic processes of pathogenic fungi. The aim of the present study was to investigate the underlying mechanisms of the reduction in number of peroxisomes in Fusarium graminearum consequent to FgPex4 and FgPex22-like deletion. The number of peroxisomes decreased by 40.55% and 39.70% when FgPex4 and FgPex22-like, respectively, were absent. Peroxisome biogenesis-related proteins, as well as inheritance- and division-related dynamin-like proteins were reduced at the transcriptional level in the mutant strains. In addition, the degree of pexophagy was intensified and the accumulation of ubiquitinated FgPex5 was also increased in F. graminearum when FgPex4 or FgPex22-like was absent. The findings suggest that FgPex4 and FgPex22-like influence the number of peroxisomes by influencing peroxisome biogenesis and pexophagy.

The A286 iron-based superalloy has wide-ranging applications in replacing expensive nickel-based and cobalt-based superalloy to manufacture the turbine disk as well as the pipelines and valves of the fourth-generation supercritical water reactor (SCWR) working below 650 °C. The recrystallization texture importantly affects the mechanical properties and oxidation resistance of superalloys. However, very few investigations are available on the recrystallisation texture of A286 alloy. The current work reports the texture of A286 alloy fabrication using various rolling routes, including one-stage cold rolling with the rolling rates of 83% (Route I) and 91% (Route II), and two-stage cold rolling with the rolling rate of 83% + 50% (Route III). Route III is preferentially recommended to manufacture A286 alloy thin plates due to the obviously reduced work hardening as well as the weakened recrystallization texture and anisotropy; moreover, compared with other routes, the recrystallized grain size of Route III did not significantly coarsen. We also revealed the mechanism for the effect of cold rolling textures on the final recrystallization texture and the role of the deformation twin in {110} grain. In this study, recrystallization texture develops through two independent mechanisms related to different deformation microstructures, including the recrystallization texture inherited from deformation texture and the recrystallization texture depended on deformation twins.

Objectives: This study further compared the endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic transcystic common bile duct exploration (LTCBDE) approaches in the treatment of common bile duct stones (CBDS) from the perspective of efficacy, safety and economy.Methods: The therapeutic efficacy and safety of ERCP and LTCBDE approaches were retrospectively compared. Cost-effectiveness analysis of clinical economics was performed to analyze and evaluate the two approaches.Results: There was no significant difference in the success rate of surgery and bile stone residue between ERCP and LTCBDE group. The incidence of postoperative complications in ERCP group was significantly higher than that in the LTCBDE group; while the incidence of pancreatitis in the ERCP group was significantly higher than that in the LTCBDE group. There was no significant difference in biliary infection, bile leakage and sepsis between ERCP and LTCBDE groups. In terms of cost, the costs of surgery and nursing were significantly lower, the costs of treatment and sanitary materials were significantly higher in the ERCP group than that in the LTCBDE group. There was no significant difference in the costs of medical examination, laboratory test, medicine cost and total cost between ERCP group and LTCBDE group. The total length of hospital stay, length of hospital stay before surgery and duration of surgery in the ERCP group were significantly lower than that in the LTCBDE group; there was no significant difference in length of hospital stay after surgery between the ERCP and LTCBDE group. The cost-effectiveness ratio of ERCP group was 34171.25, and the cost-effectiveness of LTCBDE group was 34524.25. The incremental cost-effectiveness ratio (ICER) of the two groups was 51415.Conclusion: ERCP and LTCBDE approaches had similar therapeutic efficacy in the treatment of CBDS. The safety of LTCBDE approach is superior to that of ERCP approach for the treatment of CBDS. ERCP approach is more economical in the treatment of CBDS than LTCBDE approach.

BackgroundThe prognostic role of body mass index (BMI) in patients with brain metastases is controversial. We aim to investigate the impact of BMI on prognosis and anti-cancer therapy effectiveness in brain metastases.MethodsPatients diagnosed with brain metastases between Oct 2010 and July 2019 were followed for mortality through April 2021. The prognostic role of BMI on overall survival was assessed by a restricted cubic spline (RCS) using a flexible model to visualize the relationship between the BMI values and hazard ratios of all-cause mortality, followed by a cox regression model. The disparity of survival outcomes in patients receiving anti-cancer therapies or those did not was evaluated according to the classification of BMI.ResultsA total of 2,466 patients were included in the analysis, including 241 in the underweight (BMI < 18.5 kg/m2) group, 1,503 in the normal weight group (BMI 18.5–23.9 kg/m2), and 722 in the overweight (BMI ≥ 24 kg/m2) group. Relative to the normal weight group, underweight patients were associated with poor prognosis (adjusted HR 1.25, 95% CI 1.07–1.46, p = 0.005). However, those in the overweight group showed similar overall survival when compared to the normal-weight group. Patients with weight loss were associated with a higher risk of mortality compared with patients without significant weight loss. In underweight patients, there was an insignificant difference in survival outcomes whether they received anti-cancer therapies or not.ConclusionUnderweight and significant weight loss were associated with poor prognosis in brain metastases. Meanwhile, anti-cancer therapies did not significantly improve overall survival in patients with underweight. These findings suggest that improving nutrition to maintain body weight is critical for patients with brain metastases.

Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

Abstract Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P

To improve the electrocatalytic transformation of carbon dioxide (CO2) to multi-carbon (C2þ) products is of great importance. Here we developed a nitrogen-doped Cu catalyst, by which the maximum C2þ Faradaic efficiency can reach 72.7% in flow-cell system, with the partial current density reaching 0.62 A cm-2. The in situ Raman spectra demonstrate that the *CO adsorption can be strengthened on such a N-doped Cu catalyst, thus promoting the *CO utilization in the subsequent C--C coupling step. Simultaneously, the water activation can be well enhanced by N doping on Cu catalyst. Owing to the synergistic effects, the selectivity and activity for C2þ products over the N-deoped Cu catalyst are much improved. [ABSTRACT FROM AUTHOR]

Abstract Background Cortical bone trajectory (CBT) has been well-known in spine surgery for obtaining improved fixation while minimizing soft tissue dissection. This study was designed to compare the bone mineral density (BMD) between the CBT and traditional trajectory (TT) by using Hounsfield unit (HU) values and identify the ideal decades of patients and the suitable lumbar segments using this CBT technology from a radiological standpoint. Methods Patients were selected randomly from an institutional database based on age (evenly distributed by a decade of life) and gender. A total of 240 healthy patients had a computed tomography (CT) scan of the chest, abdomen, and pelvis. For each patient, axial slices of every vertebra were cut in two planes: one horizontal to the pedicle representing the plane wherein pedicle screws were inserted using the TT and the other in a caudocranial plane representing the plane wherein pedicle screws were inserted using the CBT. For each trajectory, a region of interest (ROI) was selected within the area wherein the screws were inserted. A CT number (HU values) was then calculated within each ROI to represent bone density. Results HU values measured at the ROI of CBT were significantly greater than those of the traditional pedicle screw in all age groups, and the specific value (ratio of the HU values of CBT/the HU values of TT) between CBT and TT was 1.92. A significant difference was observed between male and female. The HU values of CBT and TT of males were generally higher than those of females (males: CBT/TT 1.89 ± 0.45; Females: CBT/TT 1.95 ± 0.47). The specific value in HU values significantly increased with increasing age (p = 0.000) and cauda lumbar level (p = 0.000) in males and females. Conclusion BMD, as measured by HU values for the ROI of the CBT screw, was significantly greater than that of the traditional pedicle screw, especially in old patients and cauda lumbar segments.

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous BRCA2 somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with BRCA-mutant pancreatic SCC.

Nowadays, an express/local mode has be studied and applied in the operation of urban rail transit, and it has been proved to be beneficial for the long-distance travel. The optimization of train patterns and timetables is vital in the application of the express/local mode. The former one has been widely discussed in the various existing works, while the study on the timetable optimization is limited. In this study, a timetable optimization model is proposed by minimizing the total passenger waiting time at platforms. Further, a genetic algorithm is used to solve the minimization problems in the model. This study uses the data collected from Guangzhou Metro Line 14 and finds that the total passenger waiting time at platforms is reduced by 9.3%. The results indicate that the proposed model can reduce the passenger waiting time and improve passenger service compared with the traditional timetable.

Background and Objective: Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. Mesenchymal stem cells (MSCs) regulate bone mass homeostasis in AIS, which might be related to the pathogenesis of AIS. However, the mRNA–miRNA–lncRNA network linked to the regulation of the genetic pathogenesis of MSCs remains unknown.Methods: We conducted an exhaustive literature search of PubMed, EMBASE, and the Gene Expression Omnibus database to find differentially expressed genes (DEGs), differentially expressed miRNAs (DE miRNAs), and differentially expressed lncRNAs (DE lncRNAs). Functional enrichment analysis was performed through Enrichr database. Protein–protein interaction (PPI) network was constructed using STRING database, and hub genes were identified by CytoHubba. Potential regulatory miRNAs and lncRNAs of mRNAs were predicted by miRTarBase and RNA22, respectively.Results: We identified 551 upregulated and 476 downregulated genes, 42 upregulated and 12 downregulated miRNAs, and 345 upregulated and 313 downregulated lncRNAs as DEGs, DE miRNAs, and DE lncRNAs, respectively. Functional enrichment analysis revealed that they were significantly enriched in protein deglutamylation and regulation of endoplasmic reticulum unfolded protein response. According to node degree, one upregulated hub gene and eight downregulated hub genes were identified. After drawing the Venn diagrams and matching to Cytoscape, an mRNA–miRNA–lncRNA network linked to the pathogenesis of MSCs in AIS was constructed.Conclusion: We established a novel triple regulatory network of mRNA–miRNA–lncRNA ceRNA, among which all RNAs may be utilized as the pathogenesis biomarker of MSCs in AIS.

A noticeable challenge for a multi-load wireless power transfer system is to achieve stable power transfer under a dynamic change in coupling conditions. It was proposed that the parity–time symmetric wireless power transfer (PT-WPT) system can achieve stable output efficiency for a single receiver when tuned at the purely real eigenfrequency. However, in the case of higher order, PT symmetric systems usually cannot maintain the real eigenfrequency. To address the issue, a high-order PT-WPT model was established using coupled mode theory (CMT) theory in this paper, and the eigenfrequency of the multi-load PT-WPT system was analyzed. Here, we propose that, theoretically, the system can work at the purely real eigenfrequency by impedance matching. The transfer efficiency of the multi-load PT-WPT system when the system works at the real eigenfrequency was analyzed. The results of the numerical simulation show that the multi load PT-WPT system can maintain stable output efficiency under a dynamic change in coupling conditions. In the long run, our work provides a new possibility for the stable transmission of the multi-load wireless power transfer system.