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Abstract Postoperative cognitive dysfunction, a common neurological complication in the perioperative period, seriously affects patient survival and prognosis. Its high incidence has made the study of postoperative cognitive dysfunction challenging. Whether the clinical application of dexmedetomidine, a potential neuroprotective drug, can reduce the incidence of postoperative cognitive dysfunction is controversial, although several potential mechanisms by which dexmedetomidine improves postoperative cognitive dysfunction have been identified; therefore, this remains an area in need of further exploration.

Abstract Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

Abstract Background Ketone β-hydroxybutyrate (BHB) has been reported to prevent tumor cell proliferation and improve drug resistance. However, the effectiveness of BHB in oxaliplatin (Oxa)-resistant colorectal cancer (CRC) and the underlying mechanism still require further proof. Methods CRC-Oxa-resistant strains were established by increasing concentrations of CRC cells to Oxa. CRC-Oxa cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were checked following BHB intervention in vitro. The subcutaneous and metastasis models were established to assess the effects of BHB on the growth and metastasis of CRC-Oxa in vivo. Eight Oxa responders and seven nonresponders with CRC were enrolled in the study. Then, the serum BHB level and H3K79me, H3K27ac, H3K14ac, and H3K9me levels in tissues were detected. DOT1L (H3K79me methyltransferase) gene knockdown or GNE-049 (H3K27ac inhibitor) use was applied to analyze further whether BHB reversed CRC-Oxa resistance via H3K79 demethylation and/or H3K27 deacetylation in vivo and in vitro. Results Following BHB intervention based on Oxa, the proliferation, migration, invasion, and EMT of CRC-Oxa cells and the growth and metastasis of transplanted tumors in mice were suppressed. Clinical analysis revealed that the differential change in BHB level was associated with drug resistance and was decreased in drug-resistant patient serum. The H3K79me, H3K27ac, and H3K14ac expressions in CRC were negatively correlated with BHB. Furthermore, results indicated that H3K79me inhibition may lead to BHB target deletion, resulting in its inability to function. Conclusions β-hydroxybutyrate resensitized CRC cells to Oxa by suppressing H3K79 methylation in vitro and in vivo.

Abstract Objective Cemiplimab, a novel PD-1 inhibitor, exhibits significant antitumor activity against advanced non-small cell lung cancer (NSCLC). However, the cost-effectiveness of this drug for the treatment remains unclear. This study aimed to assess the cost-effectiveness of cemiplimab plus chemotherapy compared to chemotherapy for the treatment of advanced NSCLC, from the perspective of the United States payer. Methods A partitioned survival approach was developed to project the disease progression of NSCLC. Overall survival (OS) and progression-free survival (PFS) data were obtained from the EMPOWER lung 3 trial and extrapolated to estimate long-term survival outcomes. Direct medical costs and utility data were collected. The primary outcome measure, the incremental cost-utility ratio (ICUR), was used to evaluate the cost-effectiveness of cemiplimab plus chemotherapy regimen. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of the results. Results In the base-case analysis, the ICUR for cemiplimab plus chemotherapy versus chemotherapy alone was estimated to be $395,593.8 per quality-adjusted life year (QALY). OWSA revealed that the results were sensitive to Hazard ratio value, utility of PFS, and cost of cemiplimab. PSA demonstrated that cemiplimab plus chemotherapy exhibited 0% probability of cost-effectiveness.In hypothetical scenario analysis, the ICUR of two regimens was $188.803.3/QALY. OWSA revealed that the results were sensitive to the discount rate, utility, and cost of cemiplimab. PSA indicated that cemiplimab plus chemotherapy achieved at least an 11.5% probability of cost-effectiveness. Conclusion Our cost-effectiveness analysis suggests that, at its current price, cemiplimab plus chemotherapy regimen is unlikely to be a cost-effective option compared with chemotherapy alone for advanced NSCLC patients, based on a threshold of $150,000 per QALY, from the perspective of the US payer.

Abstract Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.

Abstract As the latest and most anticipated method of tumor immunotherapy, CAR-NK therapy has received increasing attention in recent years, and its safety and high efficiency have irreplaceable advantages over CAR-T. Current research focuses on the application of CAR-NK in hematological tumors, while there are fewer studies on solid tumor. This article reviews the process of constructing CAR-NK, the effects of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on the efficacy of CAR-NK in solid tumor, and the role of CAR-NK in various solid tumor. The mechanism of action and the research status of the potential of CAR-NK in the treatment of solid tumor in clinical practice, and put forward the advantages, limitations and future problems of CAR-NK in the treatment of solid tumor.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), threatens wheat production worldwide, and resistant varieties tend to become susceptible after a period of cultivation owing to the variation of pathogen races. In this study, a new resistance gene against Pst race CYR34 was identified and predicted using the descendants of a cross between AS1676, a highly resistant Chinese landrace, and Avocet S, a susceptible cultivar. From a heterozygous plant from a F7 recombinant inbred line (RIL) population lacking the Yr18 gene, a near-isogenic line (NIL) population was developed to map the resistance gene. An all-stage resistance gene, YrAS1676, was identified on chromosome arm 1AL via bulked-segregant exome-capture sequencing. By analyzing a large NIL population consisting of 6537 plants, the gene was further mapped to the marker interval between KA1A_485.36 and KA1A_490.13, spanning 485.36–490.13 Mb on 1AL. A total of 66 annotated genes have been reported in this region. To characterize and predict the candidate gene(s), an RNA-seq was performed using NIL-R and NIL-S seedlings 3 days after CYR34 inoculation. Compared to NIL-S plants, NIL-R plants showed stronger immune reaction and higher expression levels of genes encoding pathogenesis-associated proteins. These differences may help to explain why NIL-R plants were more resistant to Pst race CYR34 than NIL-S plants. By combining fine-mapping and transcriptome sequencing, a calcium-dependent protein kinase gene was finally predicted as the potential candidate gene of YrAS1676. This gene contained a single-nucleotide polymorphism. The candidate gene was more highly expressed in NIL-R than in NIL-S plants. In field experiments with Pst challenge, the YrAS1676 genotype showed mitigation of disease damage and yield loss without adverse effects on tested agronomic traits. These results suggest that YrAS1676 has potential use in wheat stripe rust resistance breeding.

Degradation of shoots, characterized by stunted growth and signs of water deficit, is common in bamboo stands. However, the specific mechanisms underlying water utilization in degrading shoots remain unclear. This study sought to address this gap by harvesting bamboo shoots and culms of Phyllostachys edulis ‘Pachyloen’, employing cytological and physiological techniques to compare water utilization mechanisms between healthy and degrading shoots, and investigating the water supply to bamboo shoots by the parent bamboo. The water pressure in the degrading shoots was markedly lower compared to that of the healthy shoots, and it declined as the degradation progressed, resulting in reduced water content and the cessation of guttation in the degrading shoots. In conditions of water deficit, the percentage of free water in bamboo shoots decreased while the percentages of bound and semi-bound water increased, with the proportion of semi-bound water reaching as high as 88.13% in the late stages of degradation. The water potential of parent bamboo culms of different ages varied at different times of the day and during different growth stages of bamboo shoots, showing a strong association with the development of bamboo shoots. Conversely, the correlation between changes in the water potential of bamboo shoots and their degradation patterns was found to be comparatively minimal. The weakening of the connection between the bamboo shoots and the parent bamboo culms may play a significant role in the degradation of the bamboo shoots. This is evidenced by a decrease in the fluorescence intensity of the nucleus in bamboo shoots and the degradation of genetic material. This study lays the foundation for future research into the mechanisms of bamboo shoot degradation.

Abstract Vehicular safety is of considerable significance to the intelligent development of hybrid vehicles. However, the real-time stability control or reasonable torque distribution under the extreme road conditions remain a huge challenge due to the multiple uncertain parameters and difficulties to reconcile the handling and stability performance. To address the above problems for a through-the-road (TTR) 4-wheel-drive (4WD) hybrid vehicle, this study provides a handling and stability management (HSM) approach by incorporating the offline optimization rules and on-line model predictive control (MPC). Firstly, the vehicle dynamic model with seven degrees of freedom (7-DOF) is used to offline extract torque distribution rules (Offline-ETDR), and the online MPC feedback (Online-MPCF) is utilized to compensate the extra torque requirements for the poor effect under the extreme conditions. Accordingly, the offline optimization results and online correction are fused to provide the total torque demand given the real-time road condition detection. Finally, the real vehicle test are implemented to validate the effectiveness of the proposed torque coordination strategy. In comparison to the vehicle with no torque control strategy, the proposed method significantly improves the vehicle's cornering ability while also ensuring the high stability performance.

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.

Acoustic tomography utilizes sensor arrays to collect sound wave signals, enabling non-contact measurement of physical parameters within an area of interest. Compared to optical technologies, acoustic tomography offers the advantages of low cost, low maintenance, and easy installation. Current research in acoustic tomography mainly focuses on reconstruction algorithms for temperature fields, while monitoring the composition and concentration of gases is significant for ensuring safety and improving efficiency, such as in scenarios like boiler furnaces and aviation engine nozzles. In excitable gases, the speed of sound exhibits an S-shaped curve that changes with frequency, a characteristic that could be potentially useful for acoustic tomography. Therefore, this study primarily discusses the quantitative calculation of gas concentration and temperature based on the dispersion of the speed of sound. By employing graphic processing and pattern matching methods, a coupled relationship of the dispersion of the speed of sound with gas concentration and temperature is established. The projection intersection method is used to calculate the concentration and temperature of binary and ternary gas mixtures. Combined with the inversion method, a joint reconstruction method for gas concentration fields and temperature fields based on the dispersion of the speed of sound is developed. The feasibility of the proposed simultaneous reconstruction method for temperature and concentration fields is validated using numerical simulations. Additionally, an acoustic tomography experimental system was set up to conduct reconstruction experiments for binary gas concentration fields and temperature fields, confirming the effectiveness of the proposed method.

Abstract Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in‐depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT‐related studies.

Mn (Manganese, Mn) is an essential trace element involved in various biological processes such as the regulation of immune, nervous and digestive system functions. However, excessive Mn exposure can lead to immune damage. Occupational workers in cement and ferroalloy manufacturing and other related industries are exposed to low levels of Mn for a long time. Mn exposure is one of the important occupational hazards, but the research on the effect of Mn on the immune system of the occupational population is not complete, and there is no reliable biomarker. Therefore, this study aimed to evaluate the immunotoxicity of Mn from the soluble immune checkpoint TIM-3 (T-cell immunoglobulin and mucin containing protein 3, TIM-3) and complement C3. A total of 144 Mn-exposed workers were recruited from a bus manufacturing company and a railroad company in Henan Province. An inductively coupled plasma mass spectrometer was used to detect the concentration of RBC Mn (Red blood cell Mn, RBC Mn), and ELISA kits were used to detect serum complement C3 and TIM-3. Finally, the subjects were statistically analyzed by dividing them into low and high Mn groups based on the median RBC Mn concentration. We found that Mn exposure resulted in elevated serum TIM-3 expression and decreased complement C3 expression in workers; that serum TIM-3 and complement C3 expression showed a dose–response relationship with RBC Mn; and that the mediating effect of complement C3 between RBC Mn and TIM-3 was found to be significant. The above findings indicate that this study has a preliminary understanding of the effect of Mn exposure on the immune system of the occupational population exposed to Mn, and complement C3 and TIM-3 may be biomarkers of Mn exposure, which may provide clues for the prevention and control of Mn occupational hazards.

Long non-coding RNAs (LncRNAs) play essential roles in multiple physiological processes including bone formation. Investigators have revealed that LncRNAs regulated bone formation through various signaling pathways and micro RNAs (miRNAs). However, several problems exist in current research studies on osteogenic LncRNAs, including sophisticated techniques, high cost for in vivo experiment, as well as low homology of LncRNAs between animal model and human, which hindered translational medicine research. Moreover, compared with gene editing, LncRNAs would only lead to inhibition of target genes rather than completely knocking them out. As the studies on osteogenic LncRNA gradually proceed, some of these problems have turned osteogenic LncRNA research studies into slump. This review described some new techniques and innovative ideas to address these problems. Although investigations on osteogenic LncRNAs still have obtacles to overcome, LncRNA will work as a promising therapeutic drug for osteoporosis in the near future.

Digitate shallow-water deltas are commonly found in modern lakes and bays, as well as within cratonic petroliferous basins. They develop one or multiple sinuous finger-like sands (i.e., bar fingers), including high-RSI (sinuosity ratio of distributary channel and bar finger ≥1) and low-RSI (RSI < 1) types. Bar fingers consist of four types of subenvironments, that is, distributary channels, point bars, mouth bars, and levees. However, the internal architecture within the above subenvironments is still unclear. This paper documents the internal architecture of a digitate delta based on the integration of shallow-core and ground-penetrating radar data from the Ganjiang Delta, China, coupled with Delft3D simulations. Our results show that multiple convex-up muddy-silty accretion beds are developed in mouth bars, which top lap the side of the distributary channels or point bars and down lap the bottom of the mouth bar. The accretion beds have low dip angles (10°) compared with those in the supplying river. This dip angle exhibits a negative relationship with downstream distance and a positive exponential relationship with lateral migration distance. Silty drapes become dense along the migration direction of the distributary channel. The levee develops multiple horizontal muddy accretion beds. The high-RSI bar finger develops a large number (>3) of accretion beds in mouth bars with high dip angles, and a large number of accretion beds in thick levees, compared with the low-RSI bar finger. The results of this paper provide insights into the prediction and development of cratonic digitate shallow-water delta reservoirs.

This research examined the effects of principal transformational leadership on teachers’ inclusive teaching behaviour, with a particular inquiry into the mediating effects of teachers’ inclusive role identity and efficacy for inclusive practice, as informed by identity theory and social cognitive theory. Structural equation modelling with bootstrapping estimation was conducted using data from 712 teachers delivering inclusive teaching in primary or secondary schools in China. The results revealed the sequentially mediating mechanisms of teachers’ inclusive role identity and efficacy underlying the principal transformational leadership effects on teachers’ inclusive teaching behaviour. Research implications are also discussed.

Non-structural carbohydrates (NSCs) required for bamboo shoot development, the critical stage that determines the yield of a bamboo stand, originate from the parent bamboo with the complex underground system. However, the metabolic mechanism of NSCs in the rhizome–culm system during bamboo shoot development remains unclear. In this study, we focused on the changes of NSCs in the rhizome–culm system and used anatomical, physiological, and biochemical methods to investigate the metabolism of NSCs in bamboo shoots of Phyllostachys edulis and the role of NSCs supply in the parent bamboo at different ages. The results showed that NSCs were accumulated and consumed from the bottom to the top in a bamboo shoot, which was consistent with the developmental pattern. The starch granules were stored in advance. The bamboo sheath stored starch from the dormant stage of shoot buds. The functions of culms and rhizomes showed age-dependent differences. Adult culms showed the highest capacity to provide NSCs, with more stored NSCs and higher β-amylase activity. Conversely, young culms seemed to prefer their growth, while old culms tended to store starch. Accordingly, adult rhizomes preferred sugar transport due to the lowest starch storage, lower ADP-glucose pyrophosphorylase (AGPase) activity, and higher β-amylase activity, while young and old rhizomes tended to prefer starch storage. These results provide a basis for further understanding of nutrient metabolism in bamboo stands.

Abstract Introduction Sevoflurane acts as a gamma‐aminobutyric acid subtype A receptor agonist and can induce widespread apoptosis of immature dentate granule cells in postnatal day 21 mice. The dentate granule cells of postnatal day 21 mice undergo a developmental stage when gamma‐aminobutyric acid (GABA) shifts from inducing the depolarization of neurons to causing hyperpolarization. However, it is unclear whether sevoflurane induces apoptosis of immature granule cells by facilitating the depolarization or hyperpolarization of neurons. Methods We utilized bumetanide, an Na+–K+–2Cl− cotransporter isoform 1 (NKCC1) antagonist, to determine whether the NKCC1‐mediated GABA depolarization of neurons plays a role in sevoflurane‐induced neuroapoptosis. We also investigated whether sevoflurane exposure is related to long‐term cognitive dysfunction in postnatal day 21 mice and explored the possible protective effects of bumetanide. Results Bumetanide attenuated the sevoflurane‐induced apoptosis of dentate granule cells in postnatal day 21 mice. Exposure to sevoflurane at postnatal day 21 mice did not affect their motor ability or anxiety level, and it had no effect on spatial learning or memory functions. However, sevoflurane exposure at postnatal day 21 impaired the pattern separation ability in the contextual fear discrimination test; bumetanide mitigated this effect of sevoflurane as well. Conclusion Bumetanide attenuates sevoflurane‐induced apoptosis and is a promising prospect for protecting against anesthesia‐induced neurotoxicity in the developing brain.

Surface reconstruction is a promising approach to obtain highly efficient electrocatalysts for oxygen evolution reaction (OER), which is vital for many renewable energy conversion and storage processes. Herein, we synthesized CoFe based difluoride by a simple solvothermal treatment process with the assistance of an ionic liquid ([Bmim]BF4). The final sample originated from Co0.67Fe0.33F2 demonstrated the highest electrocatalytic activity, generating a current density of 10 mA/cm2 at an overpotential of 270 mV. The appropriate amount of iron dopant can increase the number of active sites. Besides, the in-situ leaching of fluorine accompanied with OER was found to generate metal oxyhydroxide layer with abundant oxygen vacancies, thus leading to the high performance of the electrocatalysts.

Volumetric muscle loss (VML) injuries characterized by critical loss of skeletal muscle tissues result in severe functional impairment. Current treatments involving use of muscle grafts are limited by tissue availability and donor site morbidity. In this study, we designed and synthesized an implantable glycosaminoglycan-based hydrogel system consisting of thiolated hyaluronic acid (HA) and thiolated chondroitin sulfate (CS) cross-linked with poly(ethylene glycol) diacrylate to promote skeletal muscle regeneration of VML injuries in mice. The HA-CS hydrogels were optimized with suitable biophysical properties by fine-tuning degree of thiol group substitution to support C2C12 myoblast proliferation, myogenic differentiation and expression of myogenic markers MyoD, MyoG and MYH8. Furthermore, in vivo studies using a murine quadriceps VML model demonstrated that the HA-CS hydrogels supported integration of implants with the surrounding host tissue and facilitated migration of Pax7+ satellite cells, de novo myofiber formation, angiogenesis, and innervation with minimized scar tissue formation during 4-week implantation. The hydrogel-treated and autograft-treated mice showed similar functional improvements in treadmill performance as early as 1-week post-implantation compared to the untreated groups. Taken together, our results demonstrate the promise of HA-CS hydrogels as regenerative engineering matrices to accelerate healing of skeletal muscle injuries.

Laws and policies, no matter how well designed, can fail if they are not implemented correctly. This can occur when there is no interaction between policymakers and those who are working on the ground. The purpose of this study was to determine the understanding of Chinese stakeholders regarding legislation, policy, and law associated with the provision of special education and explore its implications for student wellbeing and mental health. Two questions were posed: (1) Does a stakeholder’s attitude towards legislation, policy, and law regarding special education impact their role or responsibilities? (2) In what ways do stakeholders interact with legislation, laws, and policies regarding special education and their work experience in the field? Using in-depth interviews as the basis for the study, researchers gained valuable insight into how administrators, practitioners, and academics perceive laws and policies. Participants exhibited exaggerated attitudes and over-interpretations of some of these items, which we attribute to partly real factors, as well as nationalistic or patriotic feelings. The evidence included calls for specific laws and policies as well as a switch from a top-down to a bottom-up approach to reform to bridge the disparity between different regions in the country. As the participants agreed, there have also been remarkable achievements in building a more comprehensive and inclusive system over the last decade. However, the gaps between rural and urban areas, primary and middle schools, high schools and vocational schools need to be addressed urgently in specific laws and policies. Addressing these disparities will not only improve the overall quality of special education but also have significant implications for student wellbeing and mental health. By ensuring that all students have access to tailored support and resources, policymakers can foster a more inclusive and supportive environment that promotes positive mental health outcomes for all learners.

The numerical method was used to study bubble sliding characteristics and dynamics of R134a during subcooled flow boiling in a narrow gap. In the numerical method, the volume of fraction (VOF) model, level set method, Lee phase change model and the SST k − ω turbulent model were adopted for the construction of the subcooled flow boiling model. In order to explore bubble sliding dynamics during subcooled flow boiling, the bubble sliding model was introduced. The bubble velocity, bubble departure diameter, sliding distance and bubble sliding dynamics were investigated at 0.2 to 5 m/s inlet velocities. The simulation results showed that the bubble velocity at the flow direction was the most important contribution to bubble velocity. Additionally, the bubble velocity of 12 bubbles mostly oscillated with time during the sliding process at 0.2 to 0.6 m/s inlet velocities, while the bubble velocity increased during the sliding process due to the bubble having had a certain inertia at 2 to 5 m/s inlet velocities. It was also found that the average bubble velocity in flow direction accounted for about 80% of the mainstream velocities at 0.2 to 5 m/s. In the investigation of bubble sliding distance and departure diameter, it was concluded that the ratio of the maximum sliding distance to the minimum sliding distance was close to two at inlet velocities of 0.3 to 5 m/s. Moreover, with increasing inlet velocity, the average sliding distance increased significantly. The average bubble departure diameter obviously increased from 0.2 to 0.5 m/s inlet velocity and greatly reduced after 0.6 m/s. Finally, the investigations of the bubble sliding dynamics showed that the surface tension dominated the bubble sliding process at 0.2 to 0.6 m/s inlet velocities. However, the drag force dominated the bubble sliding process at 2 to 5 m/s inlet velocities.

RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses.

This paper develops a novel sliding mode control technology and a comprehensive evaluation methodology for speed control of permanent magnet synchronous motor (PMSM). In most of the existing literature, only control precision of the speed corrector is investigated. However, the control strategy should be stable to the noise and disturbance caused by the environment and parameter uncertainties. In order to possessing faster dynamic response, stronger anti-interference ability and high stability of input, a highly stable sliding surface is proposed for siding mode control. Unlike most of reaching laws that requires the variation of designed sliding surfaces, this method takes state vectors in consideration. In addition, a comprehensive evaluation algorithm is presented to obtain reasonable assessment on speed control for synchronous PMSMs in different operating phases (starting, transient, steady-state rating). Finally, the simulation results verify the effectiveness and validity of the proposed sliding mode speed controller.

Summary: Osteoporosis has become a high incident bone disease along with the aging of human population. Long noncoding RNAs (LncRNAs) play an important role in osteoporosis incidence. In this study, we screened out an LncRNA negatively correlated with osteoblast differentiation, which was therefore named Lnc-DIF (differentiation inhibiting factor). Functional analysis proved that Lnc-DIF inhibited bone formation. A special structure containing multiple 53 nucleotide repeats was found in the trailing end of Lnc-DIF. Our study suggested that this repeat sequence could sequester multiple miR-489-3p and inhibit bone formation through miR-489-3p/SMAD2 axis. Moreover, siRNA of Lnc-DIF would rescue bone formation in both aging and ovariectomized osteoporosis mice. This study revealed a kind of LncRNA that could function as a sponge and regulate multiple miRNAs. RNA therapy techniques that target these LncRNAs could manipulate its downstream miRNA-target pathway with significantly higher efficiency and specificity. This provided potential therapeutic insight for RNA-based therapy for osteoporosis.

Spiral ganglion neurons (SGNs) can be injured by a wide variety of insults. However, there still is a lack of degeneration models to specifically damage the SGNs without disturbing other types of cells in the inner ear. This study aims to generate an SGN-specific damage model using the Cre-LoxP transgenic mouse strains. The Cre-inducible diphtheria toxin receptor (iDTR+/+) knock-in mouse strain was crossed with a mouse strain with Cre activity specific to neurons (NeflCreER/CreER). Expression of the Cre-recombinase activity was evaluated using the reporter mouse strain Ai9 at pre-hearing, hearing onset, and post-hearing stages. Accordingly, heterozygous NeflCreER/+;iDTR+/– mice were treated with tamoxifen on postnatal days 1–5 (P1–5), followed by diphtheria toxin (DT) or vehicle injection on P7, P14, and P21 to evaluate the SGN loss. Robust tamoxifen-induced Cre-mediated Ai9 tdTomato fluorescence was observed in the SGN area of heterozygous NeflCreER/+;Ai9+/– mice treated with tamoxifen, whereas vehicle-treated heterozygote mice did not show tdTomato fluorescence. Compared to vehicle-treated NeflCreER/+;iDTR+/– mice, DT-treated NeflCreER/+;iDTR+/– mice showed significant auditory brainstem response (ABR) threshold shifts and SGN cell loss. Hair cell count and functional study did not show significant changes. These results demonstrate that the NeflCreER/CreER mouse strain exhibits inducible SGN-specific Cre activity in the inner ear, which may serve as a valuable SGN damage model for regeneration research of the inner ear.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive polyphagous species that targets many economically important fruits and vegetables. The primary control of B. dorsalis relies mainly on the use of synthetic chemicals, and excessive use of these chemicals has adverse effects on both the environment and human health. Environmentally friendly management of pests involving plant essential oils is useful for controlling the populations of pests responsible for decreasing the yields and quality of crops. In the present study, we demonstrate that clove bud essential oil (CBEO) is strongly attractive to sexually mature males. Mature males responded to the CBEO differently throughout the day; the strongest response was elicited during the day and decreased at dusk. Virgin and mated mature males did not respond differently to CBEO. No obvious response behaviour to the CBEO was observed in two species of beneficial natural predator ladybirds. In addition, a cytotoxicity assessment demonstrated that CBEO is nontoxic to normal human and mouse cells. Based on our laboratory experiments, CBEO may serve as a promising, sustainable, and environmentally friendly attractant for B. dorsalis males; however, field experiments are needed to confirm this hypothesis.

Iterative learning scheme is proposed with the aim to achieve perfect tracking of a prescribed reference trajectory for systems that operate repetitively. In this paper, a sensor fault estimation framework is proposed for nonlinear repetitive system. First, the problem of sensor fault estimation is converted to actuator fault estimation via state redefinition. Afterward, state observer is designed for state reconstruction while iterative learning law is presented for fault estimation. Thus, the information in the previous period can be utilized to improve the fault estimating performance in current iterative trial. Avoiding the uncertainty caused by the norm optimal theory, the uniform convergence of error extended system is guaranteed by asymptotic stability and optimal function. Finally, the efficiency and merits of the proposed scheme are illustrated by numerical examples.

Summary: Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment.

Regeneration of skeletal muscles is limited in cases of volumetric muscle loss and muscle degenerative diseases. Therefore, there is a critical need for developing strategies that provide cellular and structural support for skeletal muscle regeneration. In the present work, a bioengineered cell niche composed of mechanically competent aligned polyester fiber scaffolds is developed to mimic the oriented muscle fiber microenvironment by electrospinning poly(lactide-co-glycolide) (PLGA) using a custom-designed rotating collector with interspaced parallel blades. Aligned fiber scaffolds with fiber diameters ranging from 335 ± 154 nm to 3013 ± 531 nm are characterized for their bioactivities in supporting growth and differentiation of myoblasts. During in vitro culture, polymeric scaffolds with larger fiber diameter support enhanced alignment, growth, and differentiation of myoblasts associated with phosphorylation of p38 MAPK and upregulated expression of myogenin and myosin heavy chain. In vivo studies using a dystrophin-deficient mdx mouse model show that optimized fiber scaffolds seeded with primary myoblasts result in formation of dystrophin-positive myofibers network in tibialis anterior muscles. Collectively, these experiments provide critical insights on harnessing interactions between muscle cells and engineered fiber matrices to develop effective biomaterials for accelerated muscle regeneration.

Brown adipose tissues (BAT) burn lipids to generate heat through uncoupled respiration, thus representing a powerful target to counteract lipid accumulation and obesity. The tumor suppressor liver kinase b1 (Lkb1) is a key regulator of cellular energy metabolism; and adipocyte-specific knockout of Lkb1 (Ad-Lkb1 KO) leads to the expansion of BAT, improvements in systemic metabolism and resistance to obesity in young mice. Here we report the unexpected finding that the Ad-Lkb1 KO mice develop hindlimb paralysis at mid-age. Gene expression analyses indicate that Lkb1 KO upregulates the expression of inflammatory cytokines in interscapular BAT and epineurial brown adipocytes surrounding the sciatic nerve. This is followed by peripheral neuropathy characterized by infiltration of macrophages into the sciatic nerve, axon degeneration, reduced nerve conductance, and hindlimb paralysis. Mechanistically, Lkb1 KO reduces AMPK phosphorylation and amplifies mammalian target-of-rapamycin (mTOR)-dependent inflammatory signaling specifically in BAT but not WAT. Importantly, pharmacological or genetic inhibition of mTOR ameliorates inflammation and prevents paralysis. These results demonstrate that BAT inflammation is linked to peripheral neuropathy.

The single-celled trichomes of Arabidopsis thaliana have long served as an elegant model for elucidating the mechanisms of cell differentiation and morphogenesis due to their unique growth patterns. To identify new components in the genetic network that governs trichome development, we carried out exhaustive screens for additional Arabidopsis mutants with altered trichome morphology. Here, we report one mutant, aberrantly branched trichome1-1 (abt1-1), with a reduced trichome branching phenotype. After positional cloning, a point mutation in the SPIKE1 (SPK1) gene was identified in abt1-1. Further genetic complementation experiments confirmed that abt1-1 is a new allele of SPK1, so abt1-1 was renamed as spk1-7 according to the literatures. spk1-7 and two other spk1 mutant alleles, covering a spectrum of phenotypic severity, highlighted the distinct responses of developmental programs to different SPK1 mutations. Although null spk1 mutants are lethal and show defects in plant stature, trichome and epidermal pavement cell development, only trichome branching is affected in spk1-7. Surprisingly, we found that SPK1 is involved in the positioning of nuclei in the trichome cells. Lastly, through double mutant analysis, we found the coordinated regulation of trichome branching between SPK1 and two other trichome branching regulators, ANGUSTIFOLIA (AN) and ZWICHEL (ZWI). SPK1 might serve for the precise positioning of trichome nuclei, while AN and ZWI contribute to the formation of branch points through governing the cMTs dynamics. In summary, this study presented a fully viable new mutant allele of SPK1 and shed new light on the regulation of trichome branching and other developmental processes by SPK1.

This study aims to explore the perspectives of resource room teachers (RRTs) on their role transformation from regular education teachers to special educators and its influencing factors. Semistructured interviews were conducted with 10 RRTs from inclusive education schools in Beijing, China. This study found that the RRTs have experienced three stages of role transformation moving from confusion by the new job to conflict among multiple expectations and then to being professionalised as special educators with self-determination. They struggled with multiple roles, felt marginalised and deprofessionalised, and were dominated by a categorical perspective serving students with special educational needs. Moreover, clearly authorised full-time positions, professionalisation, administrative support, and attitudes towards inclusive education were found to be key determinants in RRTs' successful role transformation. The present study concludes that RRTs should be empowered with clear expectations of their roles and responsibilities to lead inclusive education practices in schools and guarantee a stable professional status via sustainable training.

In China, accompanying parents are a special group supporting inclusive preschool education for children with autism spectrum disorder (ASD). Although they lack professional knowledge and skills in children's education, they are required to accompany their children full-time to provide necessary and unique assistance. The present study aims to explore the experiences of accompanying parents of children with ASD in the context of Chinese inclusive preschool education. Semi-structured interviews and observations were conducted with 14 accompanying parents from an inclusive kindergarten. Results showed that the accompanying parents have transitioned across three roles -- from "caregivers" to "educators" to "right defenders." Each role transition resulted from their interaction with different elements in the environment and was aimed at increasing beneficial resources. Therefore, future policies and projects should improve the socioecological conditions of accompanying parents to promote inclusive preschool education in China.

This study was a pioneering attempt to determine the statistical effect of inclusive education teachers' self-efficacy on their work motivation. Five hundred and thirty-four inclusive education teachers in Beijing, China, participated in the study through responding to two inventories: the "Teacher Efficacy for Inclusive Practices Scale" and the "Multidimensional Work Motivation Scale." Results suggested that age, experience in teaching students with special educational needs, training, and subject taught had statistical influence on teacher self-efficacy but not on work motivation. Teacher self-efficacy made a unique positive contribution to three of the four types of work motivation examined, with efficacy in using inclusive instructions, efficacy in collaboration, and efficacy in managing behaviour demonstrating the strongest predictive effect on introjected regulation, identified regulation, and intrinsic motivation, respectively. The findings enrich the literature on self-efficacy and on work motivation in an inclusive education context, and have practical implications concerning teacher preparation for inclusive education.

The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous poloxamer–morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats’ flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the Culex™ unit for 48 h. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t1/2) was significantly longer in the PM (5.5 ± 7.2 h) than M (0.7 ± 0.8 h) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 min and Cmax was approximately three times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M versus PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t1/2 of morphine, without a significant tissue irritation.

The possible effect of the National Plan on the development of special education has not been examined, and there is no published evidence concerning both national and international readership about the realisation of this policy document in China. Given this, we conducted a before−after design study at a 7-year interval including six variables of special education: number of schools, total enrolment, new enrolment, graduates, educational personnel, and full-time teachers. The data were retrieved from the National Bureau of Statistics of China (NBSC). The results indicated two patterns of special education development in China. First, the National Plan has quantitatively affected some special education services (schools, new enrolments, educational personnel, and full-time teachers). Second, the National Plan has possibly resulted into better control of the quality of special education—evidenced by an insignificant increase in total enrolment and graduates at the two compared intervals.

Introduction: Dental caries still remains one of the most prevalent diseases worldwide. Unlike enamel caries which can be restored mainly by modulating mineral balance, the dentine caries are characterized with irreversible proteolytic disintegration of organic matrices, highlighting an urgent need to seek novel management strategies. Bio-modification of dentine matrix has been proposed as a novel and alternative approach to enhancing its biochemical and biomechanical properties. The resultant chemical stability and mechanic durability are specifically desirable for prevention and restoration of dentine caries. However, conventional cross linking agents, e.g. glutaraldehyde, formaldehyde,are unsuitable for clinical use due to marked cytotoxicity or instability over time. The Hypothesis: Previous studies revealed that Galla chinesis extract (GCE) could inhibit cariogenic microbes and positively modulate enamel de/remineralization balance, and the mechanism was directed to the polyphenols-organic matrix interaction involving hydrogen, covalent, ionic bonding and hydrophobic processes. Microbial transglutaminase (mTGase) could induce crosslinks between peptide chains and improve functional properties of food proteins by catalyzing an acyl transfer reaction through ε - (γ-glutamyl) lysine (GL bonds). Given the high organic content in dentine and universal reaction nature of GCE and mTGase, we put forward a hypothesis that these two natural products may serve as novel biocompatible bio-modifiers to improve biochemical and biomechanical properties of dentine matrices. Evaluation of the Hypothesis: The validation of our hypothesis will provide profound insights updating current therapeutic strategies against dentine caries, and pioneer novel approaches for biocompatible bio-modification of dentine matrices. Specifically, GCE and mTGase can be integrated into the root canal irrigating and dentine boding procedures, where they may generate beneficial effects on preservation of integrity of dentine as well as dentine-sealer interface.

Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors.