Search

Abstract Background Medial patellar ligament reconstruction (MPFL-R) in combination with derotational distal femoral osteotomy (DDFO) for treating recurrent patellar dislocation (RPD) in the presence of increased femoral anteversion is one of the most commonly used surgical techniques in the current clinical practice. However, there are limited studies on the clinical outcomes of MPFL-R in combination with DDFO to treat RPD in the presence of increased femoral anteversion. Purpose To study the role of MPFL-R in combination with DDFO in the treatment of RPD in the presence of increased femoral anteversion. Methods A systematic review was performed according to the PRISMA guidelines by searching the Medline, Embase, Web of Science, and Cochrane Library databases through June 1, 2023. Studies of patients who received MPFL-R in combination with DDFO after presenting with RPD and increased femoral anteversion were included. Methodological quality was assessed using the MINORS (Methodological Index for Nonrandomized Studies) score. Each study’s basic characteristics, including characteristic information, radiological parameters, surgical techniques, patient-reported outcomes, and complications, were recorded and analyzed. Results A total of 6 studies with 231 patients (236 knees) were included. Sample sizes ranged from 12 to 162 patients, and the majority of the patients were female (range, 67-100%). The mean age and follow-up ranges were 18 to 24 years and 16 to 49 months, respectively. The mean femoral anteversion decreased significantly from 34° preoperatively to 12° postoperatively. In studies reporting preoperative and postoperative outcomes, significant improvements were found in the Lysholm score, Kujala score, International Knee Documentation Committee score, and visual analog scale for pain. Postoperative complications were reported in all studies, with an overall reported complication rate of 4.7%, but no redislocations occurred during the follow-up period. Conclusion For RPD with increased femoral anteversion, MPFL-R in combination with DDFO leads to a good clinical outcome and a low redislocation rate. However, there was no consensus among researchers on the indications for MPFL-R combined with DDFO in the treatment of RPD.

The N6-methyladenosine (m6A) modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs. Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder (MDD), a common neuropsychiatric disorder with an unclear aetiology. Here, we found that the levels of the circular RNA HECW2 (circHECW2) were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress (CUS) mouse model. Notably, the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS. Furthermore, we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP, leading to an increase in Gng4 expression via m6A modifications. Our findings provide functional insight into the correlation between circHECW2 and m6A methylation, suggesting that circHECW2 may represent a potential target for MDD treatment.

This study aimed to develop an “environment-psychological” safety assessment model for urban villages. The objective was to create a comprehensive safety evaluation and identify key influencing factors. To start, establish a spatial environmental safety assessment system for urban villages, drawing on the six principles of Crime Prevention Through Environmental Design (CPTED) theory. Use Analytic Hierarchy Process and Bayesian network analysis for determining weights and scores. The research findings reveal that: 1) The safety of the spatial environment in urban villages is directly induced by factors such as “natural surveillance” and “image maintenance” while being indirectly impacted by factors like “territoriality” and “access control.” Notably, the effects of activity support and target hardening on spatial environmental safety are found to be insubstantial. 2) Z urban village in Xuzhou city has a level IV spatial environmental safety rating. Factors include line-of-sight transparency, environmental hygiene, and road layout. The proposed optimization measures include improving space layout, enhancing surveillance levels, and maintaining a favorable environment for crime prevention. This study aids decision-makers in establishing priority sequences for spatial planning during urban village renewal. The “Environment-Psychology” model enhances the explanatory power of environmental factors on psychological elements and can aid in spatial optimization strategies.

This paper considers setting different dips for different sub-faults to fit the actual rupture situation based on the fault rupture of the 2013 Lushan MS7.0 earthquake. Meanwhile, combined with the coseismic GNSS data of the Lushan earthquake, the source parameters and sliding distribution of the Lushan earthquake fault are inversed. Firstly, we use the gradient based optimizer (GBO) in nonlinear inversion to obtain the source parameters of this seismic fault. The inversion results indicate that the strike of the fault is 206.52°, the dip is 44.10°, the length is 21.92 km, and the depth is 12.79 km. To refine the sliding distribution of the seismic fault, the seismic fault is divided into 3 × 3 sub-faults. Then, we fix the central sub-fault dip of 44.10°; the dip of other sub-faults is obtained by iteration. After that, the model is further divided into a fault layer model composed of 23 × 19 sub fault slices, and using the Matlab fitting function is used to fit the dip of the 23 × 19 sub faults. Finally, the Lushan seismic fault plane is established as a shovel structure with steep upper and gentle lower, steep south and gentle north. The slip distribution inversion results indicate that the depth of the slip peak is 13 km, the corresponding maximum slip momentum is 0.67 m, the seismic moment is 1.10 × 1019 N·m and the corresponding moment magnitude is MW6.66. The results above are consistent with the research results of seismology.

The photovoltaic/thermal (PV/T) system is a promising option for countering energy shortages. To improve the performance of PV/T systems, compound parabolic concentrators (CPCs) and phase-change materials (PCMs) were jointly applied to construct a concentrating photovoltaic/thermal system integrated with phase-change materials (PV/T-CPCM). An open-air environment is used to analyze the effects of different parameters and the intermittent operation strategy on the system performance. The results indicate that the short-circuit current and open-circuit voltage are positively correlated with the solar irradiance, but the open-circuit voltage is negatively correlated with the temperature of the PV modules. When the solar irradiance is 500 W⋅m−2 and the temperature of the PV modules is 27.5 ºC, the short-circuit current and open-circuit voltage are 1.0 A and 44.5 V, respectively. Higher solar irradiance results in higher thermal power, whereas the thermal efficiency is under lower solar irradiance (136.2–167.1 W⋅m−2 is twice under higher solar irradiance (272.3–455.7 W⋅m−2). In addition, a higher mass flow rate corresponds to a better cooling effect and greater pump energy consumption. When the mass flow rate increases from 0.01 to 0.02 kg⋅s–1, the temperature difference between the inlet and outlet decreases by 1.8 ºC, and the primary energy-saving efficiency decreases by 0.53%. The intermittent operation of a water pump can reduce the energy consumption of the system, and the combination of liquid cooling with PCMs provides better thermal regulation and energy-saving effects under various conditions.

【Objective】 Vertically rotary sub-soiling tillage is a new cultivation method to improve soil water storage. In this study, the effect of its combination with saline water irrigation on water and salt movement in soil were studied. 【Method】 The experiment was conducted in a laboratory. It consisted of three salinity treatments with salt concentration of the irrigation water being 0 g/L (S1), 3 g/L (S2), and 5 g/L (S3) respectively, and two tillage treatments: conventional tillage (FG) and vertically rotary sub-soiling tillage (FL). For each treatment, we measured the movement of water and salt in the soil. 【Result】 With the increase in irrigation water salinity, regardless of tillage, irrigation water infiltration rate and advancing rate of the wetting front in the vertical direction both increased first followed by a decline, while the advancing rate in the horizontal wetting front increased steadily. Compared to FG, FL reduced the infiltration time by 8.70, 15.27 and 14.89%, and the advancing time of the horizontal wetting front by 10.00, 17.39 and 20.95%, respectively, for salinity treatment S1, S2 and S3. The Kostiakov model accurately described the relationship between the cumulative infiltration and infiltration time for the two tillage treatments with R2>0.99. After 20 days since irrigation, the soil moisture content in FL was lower than that in FG when irrigation water salinity was the same, while under the same tillage, the soil moisture content increased with irrigation water salinity, despite at insignificant levels. After 20 days since irrigation, soil desalination rate in FL was 42.95%-55.98%, compared to 32.34%-43.29% in FL. It was also found that for salinity treatment S1, S2 and S3, the average soil salinity in FL decreased by 22.38%, 18.54% and 15.68%, respectively, compared to those in FG. 【Conclusion】 Saline water irrigation combined with vertically rotary sub-soiling tillage improves irrigation water infiltration, advancing of wetting fronts, as well as soil desalination. For all treatments we compared, vertically rotary sub-soiling tillage combined with an irrigation water salinity of 3 g/L is optimal.

Abstract Background The timing of behavior and habitat use of nocturnal animals can be influenced by the lunar cycle in nature. The prevalence of artificial light at night (ALAN) has been recognized as a source of environmental pollution. The interaction between ALAN and the lunar cycle on bat behavior is important for understanding anthropogenic effects on bats. We utilized a decade (2012–2022) of acoustic monitoring data collected in North Carolina, United States, to investigate the relationship between bat activity, lunar cycle, and light pollution. We examined whether the amount of lunar illumination affected species-specific nightly activity and whether hourly bat activity patterns varied between nights with different moon phases. We further investigated if the relationship between bat activity and the lunar cycle might be altered by light pollution. Results We found that seven bat species showed activity variation across nights in relation to the amount of moon illumination when ALAN was absent. In general, bats were less active on full moon nights compared to new moon nights. Light pollution interacted with the bat–lunar relationship in five of the seven species, masking the effect of the lunar cycle. We identified delayed bat activity patterns on nights with a full or waxing moon in seven species, and light pollution altered that pattern in four species. Overall, ALAN was associated with decreased bat activity independent of lunar cycle effects. Conclusions Our study demonstrated that at a broad spatial scale, ALAN negatively affected many North American temperate bat species and altered their lunar chronobiology. As light pollution is spreading to historically dark areas and habitats, ALAN might couple with other threats, such as the white-nose syndrome or climate change, to cause cascading damage in the environment that depends on ecosystem services such as pest control provided by bats. We argue that further research and conservation actions are needed to mitigate the impact of light pollution.

Introduction Our objective was to examine the factors associated with the serum angiopoietin-2/angiopoietin-1 (Angpt-2/Angpt-1) ratio in peritoneal dialysis (PD) patients and to investigate the association between Angpt-2/Angpt-1 ratio and cardiovascular and all-cause mortality.Methods Patients on PD who were prevalent between January 2014 and April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters, serum angiopoietin-2 and angiopoietin-1 levels. Patients were dichotomized into two groups according to a median of Angpt-2/Angpt-1 ratio and followed up prospectively until the end of the study.Results A total of 325 patients were enrolled, including 168 males (51.7%) with a mean age of 56.9 ± 14.2 years and a median PD duration of 32.4 (9.8-55.9) months. Multiple linear regression showed pulse pressure (β = 0.206, p .05).Conclusions High Angpt-2/Angpt-1 ratio is an independent risk factor for cardiovascular and all-cause mortality in PD patients.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

ABSTRACTActinobacillus pleuropneumoniae (APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that Pichia pastoris-producing bovine neutrophil β-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen Mycobacterium bovis. In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-β in macrophages as well as dendritic cells (DC) and enhanced DC maturation in vitro. Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1β, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-β and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.

Background Sepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients.Methods We prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves.Results Of 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p

Abstract cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

ObjectiveThis study investigated the link between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in American adults.MethodsInformation for 6495 participants from the National Health and Nutrition Examination Survey (NHANES) 2017–2020.03 was used for this cross-sectional study. The link between TG/HDL-C ratios and NAFLD and liver fibrosis was assessed by multiple linear regression before evaluating nonlinear correlations based on smoothed curve fitting models. Stratification analysis was then applied to confirm whether the dependent and independent variables displayed a stable association across populations.ResultsTG/HDL-C ratios were positively correlated with NAFLD, with higher ratios being linked to increased prevalence of NAFLD. After adjusting for potential confounders, the odds ratios (OR) for NAFLD patients in the fourth TG/HDL-C quartile were 3.61 (95% confidence interval [CI], 2.94–4.38) (P for trend < 0.001) in comparison with those in the first quartile after adjusting for clinical variables. However, no statistical significance was noted for the ratio for liver fibrosis after adjusting for potential confounders (P for trend = 0.07). A nonlinear correlation between TG/HDL-C ratios and NAFLD was observed based on smoothed curve fitting models. However, a nonlinear relationship between the ratios and liver fibrosis was not established. In subgroup analyses, there was an interaction between smoking status and TG/HDL-C ratio in relation to the prevalence of liver fibrosis (P for interaction < 0.001).ConclusionsAmong American adults, the TG/HDL-C ratio was noted to be nonlinearly positively associated with the prevalence of NAFLD; however, this relationship was not present in liver fibrosis.

Origami structures with morphing behaviours and unique mechanical properties are useful in aerospace deployable structures, soft robots and mechanical metamaterials. Curved-crease origami, as one of the variants in the origami family, has a curve that connects two vertices as a crease compared to the straight crease counterpart. This feature couples the crease folding and facet bending during the folding process, providing versatile design space of mechanical metamaterials with tunable stiffness, multi-stability properties and morphing behaviours. However, current design techniques are mostly for simple geometries with intuitive construction, the modelling technique focuses on using the conventional finite element method, and the intrinsically complex geometries make specimens difficult to manufacture, which further hinders the development of curved-crease origami structures. Thus, it is valuable to review the state-of-the-art in curved-crease origami. This paper presents a review on the design methodology, analytical methods, and applications of curved-crease origami over the years, discusses their strengths, identifies future challenges and provides an outlook for the future development of the curved-crease origami concept.

Steel structures in long-term service are difficult to avoid corrosion and can be reinforced by carbon fiber reinforced polymer (CFRP) bonding method. To investigate the corrosion effect on the bond behavior between CFRP and steel, a modified cohesive zone model was proposed and verified by experiment. Then, a series of random corrosion morphologies controlled by the size and the shape of corrosion pit were generated. Finally, by importing the random corrosion morphologies and the corresponding cohesive parameters distributions into the model, a parametric analysis was executed. Results showed that the ultimate load of CFRP-corroded steel bonding system was sensitive to the size of corrosion pit, while the stiffness had identical sensitivities to the pit size and pit shape. The ultimate load would reach the peak value when the average pit width Wp,avg was 1.0 mm and the average pit depth-to-width ratio (Dp/Wp)avg was between 0.12 and 0.14, whereas the stiffness would reach a high level when the Wp,avg was between 1.0 mm and 1.2 mm and the (Dp/Wp)avg was between 0.12 and 0.14. Moreover, the effective bond length would reach a high level when the Wp,avg was between 1.0 mm and 1.2 mm and the (Dp/Wp)avg was about 0.10.

Building energy flexibility plays a critical role in demand-side management for reducing utility costs for building owners and sustainable, reliable, and smart grids. Realizing building energy flexibility in tropical regions requires solar photovoltaics and energy storage systems. However, quantifying the energy flexibility of buildings utilizing such technologies in tropical regions has yet to be explored, and a robust control sequence is needed for this scenario. Hence, this work presents a case study to evaluate the building energy flexibility controls and operations of a net-zero energy office building in Singapore. The case study utilizes a data-driven energy flexibility quantification workflow and employs a novel data-driven model predictive control (MPC) framework based on the physically consistent neural network (PCNN) model to optimize the building energy flexibility. To the best of our knowledge, this is the first instance that PCNN is applied to a mathematical MPC setting, and the stability of the system is formally proved. Three scenarios are evaluated and compared: the default regulated flat tariff, a real-time pricing mechanism, and an on-site battery energy storage system (BESS). Our findings indicate that incorporating real-time pricing into the MPC framework could be more beneficial to leverage building energy flexibility for control decisions than the flat-rate approach. Moreover, adding BESS to the on-site PV generation improved the building self-sufficiency and the PV self-consumption by 17% and 20%, respectively. This integration also addresses model mismatch issues within the MPC framework, thus ensuring a more reliable local energy supply. Future research can leverage the proposed PCNN-MPC framework for different data-driven energy flexibility quantification types.

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model‐based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature‐based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS‐High and CSRS‐Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS‐High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS‐Low subtype. Patients with CSRS‐Low score were characterized by prolonged survival time. Further analysis indicated that CSRS‐Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS‐High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS‐Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS‐High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature‐based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

The variety of enzyme-based biological preservatives is limited. This study evaluated the effects of glutathione peroxidase (GSH-Px) on the quality of crayfish during refrigerated storage by measuring the pH, total volatile basic nitrogen, trimethylamine, and microbial contamination in crayfish muscle simulation system. The results revealed that 0.3% GSH-Px (CK3) not only suppressed the degradation of nitrogenous substances but also decreased the contamination levels of total viable, Enterobacteriaceae, and Pseudomonas counts (P

Tubby-like proteins (TLPs) constitute a diverse multigene family found across a broad range of eukaryotic organisms, from single-celled to multicellular eukaryotes. Despite their importance, the existence of TLPs in walnuts (Juglans regia L.) has not been reported until now. In this study, we identified 12 members of the JrTLP gene family in the walnut genome, revealing a pattern of gene replication events. Notably, all JrTLPs exhibited a split gene structure, containing two to eight introns, and these genes could be divided into five distinct categories based on their evolutionary relationships. The majority of TLP proteins possess two signature domains: the F-box and Tubby domains. Subcellular localization prediction and experiments confirmed that JrTLP2 was located in the nucleus and membrane. Expression profiling revealed that multiple JrTLPs respond to a range of stimuli, including pathogen infection, hormonal treatment (such as auxin, ABA, MeJA, and GA), and abiotic stress conditions such as cold, heat, and salt. This study represents the first comprehensive identification of the walnut TLP family, providing valuable insights into the function and regulation of TLP in walnut and laying the foundation for future functional dissection, particularly in the context of stress tolerance.

Increasing research has shown that the abnormal expression of microRNA (miRNA) is associated with many complex diseases. However, biological experiments have many limitations in identifying the potential disease-miRNA associations. Therefore, we developed a computational model of Three-Layer Heterogeneous Network based on the Integration of CircRNA information for MiRNA-Disease Association prediction (TLHNICMDA). In the model, a disease-miRNA-circRNA heterogeneous network is built by known disease-miRNA associations, known miRNA-circRNA interactions, disease similarity, miRNA similarity, and circRNA similarity. Then, the potential disease-miRNA associations are identified by an update algorithm based on the global network. Finally, based on global and local leave-one-out cross validation (LOOCV), the values of AUCs in TLHNICMDA are 0.8795 and 0.7774. Moreover, the mean and standard deviation of AUC in 5-fold cross-validations is 0.8777+/−0.0010. Especially, the two types of case studies illustrated the usefulness of TLHNICMDA in predicting disease-miRNA interactions.

The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used treatment for depression are suboptimal. The anti-depression effects of traditional Chinese medicine (TCM) formulations have piqued the interest of the scientific community owing to their multi-ingredient, multi-target, and multi-link characteristics. According to the TCM theory, the functioning of the kidney is intricately linked to that of the brain. Clinical observations have indicated the therapeutic potential of the kidney-tonifying formula Erxian Decoction (EXD) in depression. This review aimed to comprehensively search various databases to summarize the anti-depression effects of EXD, explore the underlying material basis and mechanisms, and offer new suggestions and methods for the clinical treatment of depression. The clinical and preclinical studies published before 31 August 2023, were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical studies have demonstrated that EXD exhibits therapeutic properties in patients with menopausal depression, postpartum depression, and maintenance hemodialysis-associated depression. Meanwhile, preclinical studies have reported that EXD and its special chemical markers exert anti-depression effects by modulating monoamine neurotransmitter levels, inhibiting neuroinflammation, augmenting synaptic plasticity, exerting neuroprotective effects, regulating the hypothalamic-pituitary-adrenal axis, promoting neurogenesis, and altering cerebrospinal fluid composition. Thus, the anti-depression effects of EXD are mediated through multiple ingredients, targets, and links. However, further clinical and animal studies are needed to investigate the anti-depression effects of EXD and the underlying mechanisms and offer additional evidence and recommendations for its clinical application. Moreover, strategies must be developed to improve the quality control of EXD. This review provides an overview of EXD and guidance for future research direction.

ObjectivesThe impact of the Standard Protocol Items: Recommendations for Interventional Trials of Traditional Chinese Medicine (SPIRIT-TCM) Extension 2018 statement on the reporting quality of randomized controlled trial (RCT) protocols in traditional Chinese medicine (TCM) is not clear. This review aimed to assess the reporting characteristics and quality of RCT protocols involving interventions such as Chinese herbal medicine formulas (CHMF), acupuncture, and moxibustion published in the last 3 years.MethodsWe conducted an extensive search among multiple databases, including All EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid MEDLINE(R), PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for publications in English from 1 January 2020 to 10 August 2023. Two reviewers independently assessed the eligibility of the publications, extracted predetermined information, and evaluated the reporting based on the SPIRIT-TCM Extension 2018 checklist.ResultsOf the 420 eligible protocols (comprising 163 studies on CHMF, 239 on acupuncture, and 18 on moxibustion), the average reporting compliance rate was only 35.4%. Approximately half of the assessed items fell into the category of poorly reported, demonstrating a compliance rate below 65%. Notably, reporting compliance in acupuncture and moxibustion interventional studies exhibited higher scores than compliance in CHMF studies.ConclusionContinued, concerted, and coordinated efforts are required by journals, editors, reviewers, and investigators to improve the application and promotion of the SPIRIT-TCM Extension 2018 reporting guideline.

Background and objectivePsychological insulin resistance (PIR), which refers to the reluctance of diabetic patients to use insulin, is a frequently encountered clinical issue. Needle-free injection (NFI) offers advantages in terms of expediting insulin absorption and mitigating adverse reactions related to injection. To evaluate the effects of subcutaneous injection of insulin aspart 30 with NFI on PIR and insulin dosage in patients with type 2 diabetes mellitus (T2DM).MethodsSixty-four patients with T2DM participated in this randomized, prospective, open, crossover study. Insulin aspart 30 was administered subcutaneously to each subject via QS-P NFI and Novo Pen 5 (NP) successively. The effects of NFI on PIR were analyzed. Differences in insulin dosage, glycemic variability, and injection safety were compared at similar levels of glycemic control.ResultsAfter the administration of NFI, the insulin treatment attitude scale score decreased (53.7 ± 7.3 vs. 58.9 ± 10.7, p

Magneto-optical garnet shows great potential in integrated optical isolators due to its highly efficient non-reciprocity. In this work, we prepared magneto-optical lithium-modified terbium bismuth iron garnet films using the liquid phase epitaxy method and systemically investigated the effect of lithium modification on magnetic properties. We found a trace amount of lithium modification induced in-plane magnetization and a minimum in-plane driving field around 2 Oe. Meanwhile, high remanence over 70% was obtained in tensile-strain samples. Most importantly, in comparison to unmodified samples, the calculation of anisotropy demonstrated the giant reduction of growth-induced anisotropy in the Li: TbBiIG up to 105erg/cm3. It reveals a new rule of ions’ preferred occupation in dodecahedral sublattices indirectly. Furthermore, enhanced Faraday rotation in the near-infrared band was confirmed in the samples about 1 micrometer, up to 48% higher than unmodified samples. Our work shows Li:TbBiIGs enable a prime candidate material with substantial potential for integrated optical isolation applications.

The doubly non-central F distribution is a widely applied probability distribution. The cumulative distribution function (CDF) of the doubly non-central F distribution can be expressed using the infinite doubly series. In this paper, a CDF calculation method that allows for controlled precision is derived through the study of the infinite doubly series. By setting parameters, this method can provide an upper limit of error for the computed results, thereby allowing for precision control in the calculations. Experimental results demonstrate that this method achieves a good balance between computational precision and speed.

Abstract Background Female fertility declines with increased maternal age, and this decline is even more rapid after the age of 35 years. Follicular fluid (FF) is a crucial microenvironment that plays a significant role in the development of oocytes, permits intercellular communication, and provides the oocytes with nutrition. Exosomes have emerged as being important cell communication mediators that are linked to age-related physiological and pathological conditions. However, the metabolomic profiling of FF derived exosomes from advanced age females are still lacking. Methods The individuals who were involved in this study were separated into two different groups: young age with a normal ovarian reserve and advanced age. The samples were analysed by using gas chromatography–time of flight mass spectrometry (GC–TOFMS) analysis. The altered metabolites were analysed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify the functions and pathways that were involved. Results Our data showed that metabolites in exosomes from FF were different between women of young age and women of advanced age. The set of 17 FF exosomal metabolites (P ≤ 0.05) may be biomarkers to differentiate between the two groups. Most of these differentially expressed metabolites in FF were closely involved in the regulation of oocyte number and hormone levels. Conclusions In this study, we identified differences in the metabolites of exosomes from FF between women of young age and women of advanced age. These different metabolites were tightly related to oocyte count and hormone levels. Importantly, these findings elucidate the metabolites of the FF exosomes and provide a better understanding of the nutritional profiles of the follicles with age.

Abstract Background Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. Methods Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. Results circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. Conclusions Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-B pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

Abstract Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp 3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp 3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp 3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.

Frequency stepping is a widely used technique for ultrahigh-resolution synthetic aperture radar (SAR). Although reducing the burden of hardware, this technique increases the complexity of imaging algorithms due to the intersubband time offsets and intersubband errors of delay, amplitude, and phase. To address the above problems, an improved ultrahigh-resolution stepped-frequency spaceborne SAR imaging algorithm is proposed in this article. By generating subband images individually, performing intersubband error estimation based on primary points, and then synthesizing the subband images in the imaging domain, the proposed algorithm effectively avoids the problem of time offsets and significantly improves intersubband error compensation accuracy benefiting from the high SNR in the imaging domain. Besides, considering the characteristics of nonideal factors in frequency-stepped SAR, a series of error compensation methods aiming at stop-and-go approximation, ionospheric error, and tropospheric delay are integrated to the proposed algorithm. The effectiveness of the proposed algorithms is verified via computer simulations, and real data experiments are also conducted based on both an X-band spaceborne SAR system, Taijing 4-01, and a Ka-band spaceborne SAR system, Luojia 2-01.

Abstract Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P

Abstract Conversational artificial intelligence (AI), particularly AI-based conversational agents (CAs), is gaining traction in mental health care. Despite their growing usage, there is a scarcity of comprehensive evaluations of their impact on mental health and well-being. This systematic review and meta-analysis aims to fill this gap by synthesizing evidence on the effectiveness of AI-based CAs in improving mental health and factors influencing their effectiveness and user experience. Twelve databases were searched for experimental studies of AI-based CAs’ effects on mental illnesses and psychological well-being published before May 26, 2023. Out of 7834 records, 35 eligible studies were identified for systematic review, out of which 15 randomized controlled trials were included for meta-analysis. The meta-analysis revealed that AI-based CAs significantly reduce symptoms of depression (Hedge’s g 0.64 [95% CI 0.17–1.12]) and distress (Hedge’s g 0.7 [95% CI 0.18–1.22]). These effects were more pronounced in CAs that are multimodal, generative AI-based, integrated with mobile/instant messaging apps, and targeting clinical/subclinical and elderly populations. However, CA-based interventions showed no significant improvement in overall psychological well-being (Hedge’s g 0.32 [95% CI –0.13 to 0.78]). User experience with AI-based CAs was largely shaped by the quality of human-AI therapeutic relationships, content engagement, and effective communication. These findings underscore the potential of AI-based CAs in addressing mental health issues. Future research should investigate the underlying mechanisms of their effectiveness, assess long-term effects across various mental health outcomes, and evaluate the safe integration of large language models (LLMs) in mental health care.

Abstract Single-cell technologies enable the dynamic analyses of cell fate mapping. However, capturing the gene regulatory relationships and identifying the driver factors that control cell fate decisions are still challenging. We present CEFCON, a network-based framework that first uses a graph neural network with attention mechanism to infer a cell-lineage-specific gene regulatory network (GRN) from single-cell RNA-sequencing data, and then models cell fate dynamics through network control theory to identify driver regulators and the associated gene modules, revealing their critical biological processes related to cell states. Extensive benchmarking tests consistently demonstrated the superiority of CEFCON in GRN construction, driver regulator identification, and gene module identification over baseline methods. When applied to the mouse hematopoietic stem cell differentiation data, CEFCON successfully identified driver regulators for three developmental lineages, which offered useful insights into their differentiation from a network control perspective. Overall, CEFCON provides a valuable tool for studying the underlying mechanisms of cell fate decisions from single-cell RNA-seq data.

BackgroundThe major depressive disorder has high prevalence among adolescents， and non-suicidal self-injury （NSSI） behaviors frequently occur among patients， therefore， major depressive disorder in adolescents has become the researching focus.ObjectiveTo explore the effect of mentalization-based family therapy （MBFT） on depressive symptoms and NSSI behavior in adolescents with major depressive disorder， and to provide references for the rehabilitation of major depressive disorder in adolescents.MethodsA total of 90 adolescent patients with major depression disorder who met the diagnostic criteria of International Classification of Diseases， 10th edition （ICD-10） for depressive disorders and attended Wuhan Mental Health Center from January to December 2022 were selected， and were assigned into study group （n=44） and control group （n=46） using random number table method. All participants received routine intervention， based on this， study group added a 60-minute MBFT intervention once a week for 8 weeks. Before the intervention and at the end of 1st， 2nd，4th and 8th week，the two groups were assessed using Hamilton Depression Scale-24 item （HAMD-24）， General Self-Efficacy Scale （GSES）， Pittsburgh Sleep Quality Index （PSQI） and Ottawa Self-injury Inventory （OSI）.ResultsThe repeated measures analysis of variance reported a statistical main effect of time， main effect of group， and interaction effect between time and group at the baseline and the end of 1st， 2nd， 4th and 8th week of treatment in HAMD-24 score （F=69.621， 15.428， 29.623， P˂0.05）， OSI score （F=176.642， 37.682， 21.873， P˂0.05）， GSES score （F=215.236， 57.421， 27.857， P˂0.05） and PSQI score （F=268.541， 61.863， 33.867， P˂0.05）. Individual effect analysis discovered a statistical difference between study group and control group at the end of 2nd， 4th and 8th week of treatment in HAMD-24 score （t=5.567， 8.645， 6.233， P˂0.01）， OSI score （t=3.675， 11.817， 9.632， P˂0.01）， GSES score （t=23.462， 31.709， 12.750， P˂0.01） and PSQI score （t=9.664， 22.457， 9.333， P˂0.01）.ConclusionMBFT may improve depressive symptoms， NSSI behavior， sleep quality and self-efficacy in adolescents with major depressive disorder. ［Funded by 2022 Natural Science Foundation Project of Hubei Province （number， 2022CFB483）］

In order to investigate the flavor properties of commercial plant-based meat alternatives (PMAs) and the similarity of PMAs with meat products, this experiment used solid-phase microextraction (SPME) in conjunction with gas chromatography-olfactometry-mass spectrometry (GC-O-MS) to identify and analyze the volatile flavor compounds in three types of commercial PMAs and corresponding animal meat products. There were 30, 35, and 30 flavor-active substances discovered in chicken PMAs, beef PMAs, and pork PMAs, respectively. According to instrument measurement and relative odor activity value (ROAV) analysis, the key flavor components thatmade up the three types of PMAs were aldehydes, including heptanal (rubber, meat tallow), (E)-2-octenal (delicate fragrance, meat tallow), (E)-2-nonenal (meat tallow, salt, sauce), and (E,E)-2,4-decadienal (meat tallow). Key flavor components of the chicken PMAs group also included nonanal (celery), decyl aldehyde (garlic, acid), and (E)-2,4-nonadienal (meat tallow). Key flavor components up the beef PMAs group included decyl aldehyde (beany flavor, roasted onion), ethyl hydride maltol (tallow, sauce), methyl furfuryl disulfide (roasted), and (E,E)-2,4 nonadienal (meat tallow). Key flavor components of the pork PMAs group were (E)-2-undecenal (fried), (E,Z)-2,4-decadienal (sauce), and 2-acetylthiazole (bean). This study demonstrated the primary aromatic substances that contributed to the overall olfactory features of PMAs were aldehydes. During processing, the flavorings from spices had masking and imitating impact. As a result, this work provides both theoretical and empirical support for further improving and maximizing the authenticity of PMAs flavor qualities.

Abstract The ability of modern detectors to detect small targets is still an unresolved topic compared to their capability of detecting medium and large targets in the field of object detection. Accurately detecting and identifying small objects in the real‐world scenario suffer from sub‐optimal performance due to various factors such as small target size, complex background, variability in illumination, occlusions, and target distortion. Here, a small object detection method for complex traffic scenarios named deformable local and global attention (DLGADet) is proposed, which seamlessly merges the ability of hierarchical attention mechanisms (HAMs) with the versatility of deformable multi‐scale feature fusion, effectively improving recognition and detection performance. First, DLGADet introduces the combination of multi‐scale separable detection and multi‐scale feature fusion mechanism to obtain richer contextual information for feature fusion while solving the misalignment problem of classification and localisation tasks. Second, a deformation feature extraction module (DFEM) is designed to address the deformation of objects. Finally, a HAM combining global and local attention mechanisms is designed to obtain discriminative features from complex backgrounds. Extensive experiments on three datasets demonstrate the effectiveness of the proposed methods. Code is available at https://github.com/ACAMPUS/DLGADet

COVID-19 has posed formidable challenges as a significant global health crisis. Its complexity stems from factors like viral contagiousness, population density, social behaviors, governmental regulations, and environmental conditions, with interpersonal interactions and large-scale activities being particularly pivotal. To unravel these complexities, we used a modified SEIR epidemiological model to simulate various outbreak scenarios during the holiday season, incorporating both inter-regional and intra-regional human mobility effects into the parameterization scheme. In addition, evaluation metrics were used to evaluate the accuracy of the model simulation by comparing the congruence between simulated results and recorded confirmed cases. The findings suggested that intra-city mobility led to an average surge of 57.35% in confirmed cases of China, while inter-city mobility contributed to an average increase of 15.18%. In the simulation for Tianjin, China, a one-week delay in human mobility attenuated the peak number of cases by 34.47% and postponed the peak time by 6 days. The simulation for the United States revealed that human mobility played a more pronounced part in the outbreak, with a notable disparity in peak cases when mobility was considered. This study highlights that while inter-regional mobility acted as a trigger for the epidemic spread, the diffusion effect of intra-regional mobility was primarily responsible for the outbreak. We have a better understanding on how human mobility and infectious disease epidemics interact, and provide empirical evidence that could contribute to disease prevention and control measures.

Abstract Background Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N 6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. Methods Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. Results Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. Conclusions AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.

Abstract Background Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. Methods In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. Results All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P

Abstract Background Regulator of G protein signaling 5 (RGS5), as a negative regulator of G protein-coupled receptor (GPCR) signaling, is highly expressed in arterial VSMCs and pericytes, which is involved in VSMC phenotypic heterogeneity and vascular remodeling in tumors. However, its role in normal and tumor vascular remodeling is controversial. Methods RGS5 knockout (Rgs5-KO) mice and RGS5 overexpression or knockdown in VSMCs in vivo by adeno-associated virus type 9 (AAV) carrying RGS5 cDNA or small hairpin RNA (shRNA) targeting RGS5 were used to determine the functional significance of RGS5 in vascular inflammation. RGS5 expression in the triple-negative (TNBCs) and non-triple-negative breast cancers (Non-TNBCs) was determined by immunofluorescent and immunohistochemical staining. The effect of breast cancer cell-conditioned media (BC-CM) on the pro-inflammatory phenotype of VSMCs was measured by phagocytic activity assays, adhesion assay and Western blot. Results We identified that knockout and VSMC-specific knockdown of RGS5 exacerbated accumulation and pyroptosis of pro-inflammatory VSMCs, resulting in vascular remodeling, which was negated by VSMC-specific RGS5 overexpression. In contrast, in the context of breast cancer tissues, the role of RGS5 was completely disrupted. RGS5 expression was increased in the triple-negative breast cancer (TNBC) tissues and in the tumor blood vessels, accompanied with an extensive vascular network. VSMCs treated with BC-CM displayed enhanced pro-inflammatory phenotype and higher adherent with macrophages. Furthermore, tumor-derived RGS5 could be transferred into VSMCs. Conclusions These findings suggest that tumor microenvironment shifts the function of RGS5 from anti-inflammation to pro-inflammation and induces the pro-inflammatory phenotype of VSMCs that is favorable for tumor metastasis.

Abstract Learning effective molecular feature representation to facilitate molecular property prediction is of great significance for drug discovery. Recently, there has been a surge of interest in pre-training graph neural networks (GNNs) via self-supervised learning techniques to overcome the challenge of data scarcity in molecular property prediction. However, current self-supervised learning-based methods suffer from two main obstacles: the lack of a well-defined self-supervised learning strategy and the limited capacity of GNNs. Here, we propose Knowledge-guided Pre-training of Graph Transformer (KPGT), a self-supervised learning framework to alleviate the aforementioned issues and provide generalizable and robust molecular representations. The KPGT framework integrates a graph transformer specifically designed for molecular graphs and a knowledge-guided pre-training strategy, to fully capture both structural and semantic knowledge of molecules. Through extensive computational tests on 63 datasets, KPGT exhibits superior performance in predicting molecular properties across various domains. Moreover, the practical applicability of KPGT in drug discovery has been validated by identifying potential inhibitors of two antitumor targets: hematopoietic progenitor kinase 1 (HPK1) and fibroblast growth factor receptor 1 (FGFR1). Overall, KPGT can provide a powerful and useful tool for advancing the artificial intelligence (AI)-aided drug discovery process.

Abstract Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.

The wetting behaviors of Al-Si-Cu-Mg-Zn brazing materials on 5083 aluminum alloy substrate were investigated through changing the proportion of Mg from 0 to 2 wt.%. The experimental results showed that the welding process goes through the three following stages: slow spreading, fast spreading, and stabilizing. The wettability of the brazing material was improved effectively, and the porosity of the interfacial layer was reduced, with the addition of Mg. With Mg content at 1 wt.%, the wetting diameter reached a maximum value of 20.46 mm. The reaction mechanism of the wetted interfacial layer between the brazing material and substrate alloy was illustrated with dynamic data, provided through experimentation and simulated thermodynamic calculation, and showed that the wetting behavior of the resultant Al-7.5Si-15Cu-1Mg-5Zn brazing material was dominated primarily by a diffusion reaction from elemental magnesium.

With the growing world population, food demand has also increased, resulting in increased agricultural waste and livestock manure production. Wheat straw and cow dung are rich nutrient sources and, if not utilized properly, may lead to environmental pollution. Keeping in view the cultivation of Agaricus bisporus on straw/manure-based substrate, the current study aimed to optimize the conventional manure preparation technique to reduce nutrient losses and keep the quality of manure at its best. The treatments were considered as traditional and optimized schemes for mushroom substrate preparation. The results achieved herein indicated that the nutrient losses were low in the optimum scheme. For carbon (C), the loss was 43.55% at the substrate stage in the traditional scheme and reduced to 37.75% in the optimum scheme. In the case of nitrogen (N), the loss was 22.01% in the traditional scheme and was lower (18.49%) in the optimum scheme. The nutrient concentration in Agaricus bisporus was higher with the optimum scheme compared with the traditional scheme. It was 1.74% for C, 7.17% for N, 3.58% for phosphorus (P), and 4.92% for potassium (K). The optimum scheme also improved the Agaricus bisporus yield per unit area (84.55%) and the total yield (28.92%). The net income of the optimum scheme was 102.95% higher compared to the traditional scheme. The economic analysis also revealed that the benefit–cost ratio of the optimum scheme was high (48.86%) compared with the traditional scheme. This study concludes that the use of the optimum scheme can better utilize the wheat straw and cow manure waste for substrate preparation and reducing nutrient losses. In addition, the final mushroom residue can also be used as a leftover substrate for further utilization.

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage.

Fixed-wing unmanned aerial vehicles (UAVs) have the advantages of long endurance and fast flight speed and are widely used in surveying, mapping, monitoring, and defense fields. However, its conventional take-off and landing methods require runway support. Achieving runway-free recovery is necessary for expanding the application of fixed-wing UAVs. This research comprehensively reviews the various techniques and scenarios of runway-free recovery of fixed-wing UAVs and summarizes the key technologies. The above methods cover parachute recovery, net recovery, rope recovery, SideArm recovery, deep stall recovery, towed drogue docking recovery, and robotic arm recovery methods within runway-free recovery. Finally, this research discusses the future research directions of runway-free recovery.

Oil–air lubrication technology is commonly utilized in the lubrication design of traditional components to reduce friction between contact pairs. This study focuses on testing the point-contact friction pairs of two quantitative valves using a self-made oil–air lubrication traction force machine with a G95Cr18 disk and ball as the friction pairs. The test data are analyzed using a four-parameter exponential model. Additionally, a calculation model of the oil–air lubrication flow field is established, defining boundary conditions and conducting flow field simulation analysis. The results of the ball and disk test show that the traction coefficient increases with load and decreases with entrainment speed. Furthermore, when the air-speed is 12 m/s, the traction coefficient is lower for the oil supply of 6 mL/min than for the oil supply of 1.5 mL/min. According to CFD analysis, the volume fraction of the oil phase in the contact area increases with the increase of entrainment speed when the slip–roll ratio is 0.1. The theoretical values from the four-parameter exponential model align well with the experimental results, and the fitting accuracy is higher than 0.95.

BackgroundSerum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP.MethodsWe conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted.ResultsA total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups.ConclusionThe CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.

Abstract N6‐methyladenosine (m6A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion and angiogenesis are characteristic features of its TME. The role of YTH N6‐methyladenosine RNA binding protein 2 (YTHDF2), as an m6A reader, in regulating HCC TME are not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 and H3 lysine 27 acetylation modification in the promoter region of YTHDF2 enhanced its expression in HCC, and upregulated YTHDF2 in HCC predicted a worse prognosis. Animal experiments demonstrated that Ythdf2 depletion inhibited spontaneous HCC formation, while its overexpression promoted xenografted HCC progression. Mechanistically, YTHDF2 recognized the m6A modification in the 5′‐untranslational region of ETS variant transcription factor 5 (ETV5) mRNA and recruited eukaryotic translation initiation factor 3 subunit B to facilitate its translation. Elevated ETV5 expression induced the transcription of programmed death ligand‐1 and vascular endothelial growth factor A, thereby promoting HCC immune evasion and angiogenesis. Targeting YTHDF2 via small interference RNA‐containing aptamer/liposomes successfully both inhibited HCC immune evasion and angiogenesis. Together, this findings reveal the potential application of YTHDF2 in HCC prognosis and targeted treatment.

Abstract Passivating contactsin heterojunction (HJ) solar cells have shown great potential in reducing recombination losses, and thereby achieving high power conversion efficiencies in photovoltaic devices. In this direction, carbon nanomaterials have emerged as a promising option for carbon/silicon (C/Si) HJsolar cells due to their tunable band structure, wide spectral absorption, high carrier mobility, and properties such as multiple exciton generation. However, the current limitations in efficiency and active area have hindered the industrialization of these devices. In this review, they examine the progress made in overcoming these constraints and discuss the prospect of achieving high power conversion efficiency (PCE) C/Si HJ devices. A C/Si HJ solar cell is also designed by introducing an innovative interface passivation strategy to further boost the PCE and accelerate the large area preparationof C/Si devices. The physical principle, device design scheme, and performanceoptimization approaches of this passivated C/Si HJ cells are discussed. Additionally, they outline potential future pathways and directions for C/Si HJ devices, including a reduction in their cost to manufacture and their incorporation intotandem solar cells. As such, this review aims to facilitate a deeperunderstanding of C/Si HJ solar cells and provide guidance for their further development.