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Abstract Background For renal hilar angiomyolipoma, general surgical resection is often quite challenging. The aim of this study is to evaluate the safety and efficacy of an innovative robot-assisted laparoscopic strategy that combines tumor enucleation with tumor aspiration in the treatment of renal hilar angiomyolipoma. Methods The clinical data of 38 patients with renal hilar angiomyolipoma who went through robotic tumor enucleation combined with tumor aspiration in the Department of Urology, the Affiliated Hospital of Nanjing University Medical School, from December 2019 to December 2022 were retrospectively analyzed. The basic characteristics, the perioperative variables, intraoperative procedures, and postoperative complications were all recorded. Patients were followed up to evaluate the angiomyolipoma recurrence and the renal function by urologic CT or ultrasound and renal function tests. Results All surgeries were successfully completed without conversion to radical nephrectomy or open surgery. One patient developed urinary extravasation 10 days after surgery, and was readmitted to the hospital for transurethral ureteral stenting considering the injury of the renal collecting system. The median operative time was 181.5 (123.8-206.3) min, the warm ischemia time was 20.0 (17.3–24.0) min, the blood loss was 125 (100.0-262.5) ml, and no patients received blood transfusion during and after surgery. The median hospitalization time was 7.0 (6.0–9.0) days, and the duration of indwelling drainage tube was 2.0 (2.0–3.0) days. The serum creatinine (Scr) on the first day, 3 months, and 6 months after surgery were 55.5 (50.8–62.8) µmol/L, 55.5 (48.0–62.0) µmol/L and 54.0 (51.8–63.5) µmol/L, respectively, and there was no significant difference compared with the preoperative level 56.0 (47.8–60.3) µmol/L. All patients were followed up after surgery, and the urinary CT scan or renal color doppler ultrasound, and renal function were reexamined. The median follow-up time of all patients was 19.0 (14.75-33.0) months, and no local recurrence of angiomyolipoma was seen in all patients. Conclusions The surgical strategy of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration is safe and effective in the treatment of renal hilar angiomyolipoma.

Abstract Background Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. Methods This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. Ethics and dissemination The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association’s Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. Conclusions Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. Trial registration number Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Abstract Objective To investigate the value of magnetic resonance examination technique for prenatal genetic diagnosis and clinical intrauterine treatment of fetal congenital cystic adenoma (CCAM) of the lung. Methods A retrospective analysis was conducted on 108 pregnant women admitted to a certain hospital from January 2016 to January 2022 for pre natal examination and consultation on eugenics. The selected pregnant women were aged 20–40 and had a gestational age of 17–36 weeks. Ultrasound and MRI examinations were performed on 108 pregnant women who met the inclusion criteria. Follow-up and investigation were conducted on the fetus after being diagnosed with CCAM. To analyze the results of prenatal genetic diagnosis, chromosome microarray analysis (CMA) was used to analyze samples with pathogenic Copy Number Variants (CNV) and identify pathogenic genes. Finally, the imaging diagnosis results obtained through statistical software were analyzed, and the correlation between pathogenic genes and CCAM, as well as the clinical application value of MRI in fetal intrauterine treatment was explored. Results Among all cases, 68 fetuses were diagnosed with CCAM through ultrasound examination; 71 fetuses were diagnosed with CCAM through MRI examination. A total of 74 samples were confirmed as CCAM by autopsy and neonatal CT. The sensitivity, specificity, and accuracy of MRI in diagnosing fetal congenital CCAM were higher than those of ultrasound examination. The expression of CCAM was positively correlated with DUSP22, PRSS1, and SHOX, with all R values greater than 0.8. The clinical decision curve showed that when the probability of fetal CCAM was less than 0.03, the prenatal genetic diagnostic model of MRI was not applicable; But when the probability of fetal CCAM was higher than 0.05, the auxiliary intrauterine treatment effect that MRI diagnostic methods achieved was significantly better than conventional diagnosis. Conclusion MRI is significantly better than ultrasound in the diagnosis of CCAM, which can effectively improve the sensitivity of diagnosis and provide accurate information for the eugenics of pregnant women, and has high clinical application value.

Abstract Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes.

One of the main underlying etiologies of type 2 diabetes (T2DM) is insulin resistance, which is most frequently caused by obesity. Notably, the deregulation of adipokine secretion from visceral adiposity has been identified as a crucial characteristic of type 2 diabetes and obesity. Spexin is an adipokine that is released by many different tissues, including white adipocytes and the glandular stomach, and is negatively connected with the state of energy storage. This peptide acts through GALR2/3 receptors to control a wide range of metabolic processes, including inflammation, browning, lipolysis, energy expenditure, and eating behavior. Specifically, spexin can enter the hypothalamus and regulate the hypothalamic melanocortin system, which in turn balances energy expenditure and food intake. This review examines recent advances and the underlying mechanisms of spexin in obesity and T2DM. In particular, we address a range of topics from basic research to clinical findings, such as an analysis of the possible function of spexin in the hypothalamic melanocortin response, which involves reducing energy intake and increasing energy expenditure while also enhancing insulin sensitivity and glucose tolerance. Gaining more insight into the mechanisms that underlie the spexin system's control over energy metabolism and homeostasis may facilitate the development of innovative treatment approaches that focus on combating obesity and diabetes.

Abstract Successful dental pulp regeneration is closely associated with rapid revascularization and angiogenesis, processes driven by the Jagged1(JAG1)/Notch signaling pathway. However, soluble Notch ligands have proven ineffective in activating this pathway. To overcome this limitation, a Notch signaling hydrogel is developed by indirectly immobilizing JAG1, aimed at precisely directing the regeneration of vascularized pulp tissue. This hydrogel displays favorable mechanical properties and biocompatibility. Cultivating dental pulp stem cells (DPSCs) and endothelial cells (ECs) on this hydrogel significantly upregulate Notch target genes and key proangiogenic markers expression. Three‐dimensional (3D) culture assays demonstrate Notch signaling hydrogels improve effectiveness by facilitating encapsulated cell differentiation, enhancing their paracrine functions, and promoting capillary lumen formation. Furthermore, it effectively communicates with the Wnt signaling pathway, creating an odontoinductive microenvironment for pulp‐dentin complex formation. In vivo studies show that short‐term transplantation of the Notch signaling hydrogel accelerates angiogenesis, stabilizes capillary‐like structures, and improves cell survival. Long‐term transplantation further confirms its capability to promote the formation of pulp‐like tissues rich in blood vessels and peripheral nerve‐like structures. In conclusion, this study introduces a feasible and effective hydrogel tailored to specifically regulate the JAG1/Notch signaling pathway, showing potential in advancing regenerative strategies for dental pulp tissue.

Objective To retrospectively analyze the blood use of transfusion-dependent thalassemia (TDT) patients in 9 designated transfusion medical institutions from 2018 to 2023 in Nanning, and to evaluate the effect of " three designated " blood transfusion mode (hereby means TDT patients undergoing blood transfusion in designated transfusion medical institutions regularly) and " collection-based-supply" blood management mode on blood security of TDT patients. Methods The " three designated" blood transfusion mode was implemented to ensure that TDT patients registered in the local household registration (referred to as the " register" ) obtain the rights and interests of outpatient transfusion and blood security of designated medical institutions. The " collection-based-supply" blood management mode was implemented to assess the blood needs of "register" TDT patients and meet their needs to the maximum extent according to the blood inventory (collection). Results From 2018 to 2023, the total blood supply of "register" TDT patients was 10.37% of the total red blood supply of all medical institutions (138 509.5 U /1 335 788.0 U), with the highest proportion of type O blood as 46.34% (64 181.0 U/138 509.5 U) and the lowest proportion of type AB blood as 3.85% (5 331.0 U/138 509.5 U). In 2018, 9 transfusion medical institutions were designated for TDT patients.There were a total of 766 TDT patients in the register, with the per capita annual blood transfusion volume increased from 20.28 U (15 531.0 U/766 patients) in 2018 to 36.01 U (27 586.0 U/766 patients) in 2023, maintaining a positive growth every year(30.26%, 4.94%, 11.71%, 8.61%, 4.94% and 7.10%). Conclusion The " three designated" blood transfusion mode and the " collection-based-supply " blood management mode can effectively guarantee the blood supply of TDT patients.

Abstract Neuroinflammation is one of the core pathological features of Parkinson’s disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.

Abstract The YOLO series of algorithms have made substantial contributions to the detection of insulator defects in power transmission line operations. However, existing target detection algorithms for the small target detection and low‐quality insulator images encounter difficulties in effectively capturing relevant features, resulting in a higher probability of target loss. To identify and classify defects in the operational state of insulators, an improved YOLOv8 target identification algorithm called DGW‐YOLOv8 is proposed in this paper. The deformable attention backbone of the DGW‐YOLOv8 target identification algorithm is designed by adding the deformable ConvNets v2 module and the global attention mechanism. This addition reduces the feature loss caused by the network feature processing, enhances the sensitivity of the algorithm to small‐scale targets, and reduces the impact caused by the different global positions of the targets. Additionally, to address the problem of low quality of captured images, WIoU v3 is used to replace CIoU in the original YOLOv8 target identification algorithm to optimize the loss function, reduce the degrees of freedom, and improve the network robustness. Experimental results demonstrate that the enhanced YOLOv8 algorithm can achieve an improvement of 2.4% and 5.5% in mAP and mAP50‐95, respectively, compared with the original algorithm.

The outbreak of COVID-19 causes a serious threat to human health and life around the world and puts enormous pressure on the healthcare system. The lockdown policy has effectively reduced the number of cases and suppressed the spread of the COVID-19 epidemic, but it also requires high social and economic costs. In this paper, we aim to use feedback control to help decision-makers establish lockdown policies, which can effectively constrain the spread of the COVID-19 pandemic with minimal financial loss. The time-dependent susceptible-infected-removed (SIR) model is used for the dynamics of the COVID-19 pandemic. The feedback control is based on a modified nonlinear active disturbance rejection controller (ADRC) that includes modified nonlinear extended state and nonlinear state error feedback with parameters tuned by particle swarm optimization, and the performances are compared with a well-known proportional-–integral–-derivative (PID) controller. The final simulation results show that the modified nonlinear ADRC has better performances and is more robust against uncertainties in the parameters of the epidemiological model.

Underwater imaging is often affected by light attenuation and scattering in water, leading to degraded visual quality, such as color distortion, reduced contrast, and noise. Existing underwater image enhancement (UIE) methods often lack generalization capabilities, making them unable to adapt to various underwater images captured in different aquatic environments and lighting conditions. To address these challenges, a UIE method based on the conditional denoising diffusion probabilistic model (DDPM) is proposed (DiffWater), which leverages the advantages of DDPM and trains a stable and well-converged model capable of generating high-quality and diverse samples. Considering the multiple distortion issues in underwater imaging, unconditional DDPM may not achieve satisfactory enhancement and restoration results. Therefore, DiffWater utilizes the degraded underwater image with added color compensation as a conditional guide, through which the DiffWater achieves high-quality restoration of degraded underwater images. Particularly, the proposed DiffWater introduces a color compensation method that performs channelwise color compensation in the RGB color space, tailored to different water conditions and lighting scenarios, and utilizes this condition to guide the denoising process. In the experimental section, the proposed DiffWater method is tested on four real underwater image datasets and compared against existing methods. Experimental results demonstrate that DiffWater outperforms existing comparison methods in terms of enhancement quality and effectiveness, exhibiting stronger generalization capabilities and robustness.

Abstract Cesium lead triiodide (CsPbI3) perovskite receives tremendous attention for photovoltaic applications, owing to its remarkable thermal stability and optoelectronic properties. However, realizing the CsPbI3 perovskite with high black‐phase stability and optoelectronic properties remains a significant challenge, which largely affects the photovoltaic performance of perovskite solar cells (PSCs). Herein, aromatic ammonium agents are used to modulate the crystallization of the CsPbI3 perovskite to improve its black‐phase stability and optoelectronic properties for efficient PSCs. Systemically experimental studies and comprehensively theoretical calculations are performed, which reveal that histammonium dihydrochloride (HACl2) could strongly couple with the perovskite during its crystallization, leading to faster nucleation and slower perovskite growth, and thus modulating the crystallization dynamics of the perovskites. Moreover, the residual diammonium cations (HA2+) distributed at the grain boundaries and on the surface of the perovskites can effectively passivate defects through electrostatic interactions, substantially suppressing trap‐assisted nonradiative recombination, and prompting more matched perovskite surface energetics. Consequently, the photovoltaic performance of CsPbI3 PSCs is largely improved because of a combination of enhanced crystallinity and optoelectronic properties of the perovskites. This work offers a new avenue to prepare inorganic perovskites with high optoelectronic properties for photovoltaics.

Temperature estimation of interacting quantum many-body systems is both a challenging task and topic of interest in quantum metrology, given that critical behavior at phase transitions can boost the metrological sensitivity. Here we study noninvasive quantum thermometry of a finite, two-dimensional Ising spin lattice based on measuring the dephasing dynamics of a spin probe coupled to the lattice. We demonstrate a strong critical enhancement of the achievable precision in terms of the quantum Fisher information, which depends on the coupling range and the interrogation time. Our numerical simulations are compared to instructive analytic results for the critical scaling of the sensitivity in the Curie-Weiss model of a fully connected lattice and to the mean-field description in the thermodynamic limit, both of which fail to describe the critical spin fluctuations on the lattice the spin probe is sensitive to. Phase metrology could thus help to investigate the critical behavior of finite many-body systems beyond the validity of mean-field models.

This paper aims to present a comprehensive assessment of the evolution of environmental law in Puerto Rico from 1897 to 2021. The study identifies significant legislative developments, with a surge in federal and local laws post-1960, correlating with heightened environmental awareness. Political dynamics, notably party affiliations, significantly influence the level of legal protection afforded to the environment. A new classification system is introduced to analyze laws based on ecosystem and resource protection. Distinct periods of legislative activity are identified, with federal laws predominant from 1960 to 1990 and state laws from 1990 to 2021, revealing a unique pattern of legislative ''pulses.'' Federal laws primarily address coastal ecosystems and pollution mitigation, while state laws focus on land ecosystems, reserves, and resource management. The study establishes a statistically significant correlation between the passage of time and the number of enacted laws, indicating an upward trend in environmental legislation. Additionally, it highlights the impact of political parties on lawmaking, with variations in legislative output observed under different party control scenarios. The study found that the legislative output in both the US and Puerto Rico was affected by party control. Specifically, when the Republican Party or the local Popular Democratic Party controls the House of Representatives or the Senate, the output of environmental legislation decreases. On the other hand, the study suggests that the US President's party identity has a lesser effect on enacting environmental laws. The study underscores the intricate relationship between politics and environmental policy, emphasizing the significance of political dynamics in shaping environmental law. The findings offer valuable insights for policymakers, environmentalists, and stakeholders, aiding in developing more effective strategies for sustainable development and conservation in Puerto Rico. Recommendations include utilizing the comprehensive table of environmental regulations to detect agency overlaps and investigate the correlation between legal protection and ecosystem health.

Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60–1.50 d), Interval from First Service to Conception (FSTC, 0.20–16.20 d), Calving Interval (CI, 4.00–7.00 d), and Number of Services (NUMS, 0.07–0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding.

Power consumers can obtain authoritative green environmental value certification through green electricity trading, which plays an important role in improving the production competitiveness of enterprises, especially for international product trade affairs. However, the credibility of green electricity transactions faces serious challenges in the enterprise green authentication affairs, especially the user’s identity authentication, the traceability of green electricity transactions, and the standardization of green electricity transactions. Aiming to solve the certification and traceability problem of tradable green certificates, this paper proposes an integrated green certificate trading protocol, which solves its double-trading problem and helps to improve the credibility of renewable energy use. The main contribution is providing a solution based on the consortium blockchain technology to solve the main challenges mentioned above. The main solved scheme designs a series of protocols, which includes a purchase protocol, payment protocol, and non-transferable protocol. The whole process ensures the credibility, traceability, and non-transferability of green certificate trading. Multiple verification measures are adopted to address security and privacy challenges in green certificate management. Through security analysis, the protocol effectively defends against attacks such as double payments, transaction rollback, and transaction replays while ensuring users’ privacy.

Graphene has been considered an ideal reinforcement in aluminum alloys with its high Young’s modulus and fracture strength, which greatly expands the application range of aluminum alloys. However, the dispersion of graphene and the interfacial reaction between graphene and the aluminum matrix limit its application due to elevated temperature. Friction stirring processing (FSP) is regarded as a promising technique to prepare metal matrix composites at lower temperatures. In this paper, FSP was used to prepare graphene-nanoplates-reinforced aluminum composites (GNPs/Al). The corresponding effects of the process parameters and graphene content on GNPs/Al were thoroughly studied. The results showed that plastic strain, heat input, and graphene content were the key influencing factors. Large degrees of plastic strain can enhance the dispersion of graphene by increasing the number of stirring passes and the ratio of stirring to welding velocity, thereby improving the strength of GNPs/Al. Low heat input restricts the plastic flow of graphene in the matrix, whereas excessive heat input can promote interfacial reactions and lead to the formation of a more brittle phase, Al4C3. This is primarily associated with the stirring velocity and welding velocity. High graphene content levels can improve the material strength by refining the grain size, improving the load transfer ability, and acting as a precipitate to prevent dislocation movement. These findings make a contribution to the development of advanced aluminum alloys with graphene reinforcement, offering broader application potential in industries.

Unmanned surface vessel (USV) target detection algorithms often face challenges such as misdetection and omission of small targets due to significant variations in target scales and susceptibility to interference from complex environments. To address these issues, we propose a small target enhanced YOLOv7 (STE-YOLO) approach. Firstly, we introduce a specialized detection branch designed to identify tiny targets. This enhancement aims to improve the multi-scale target detection capabilities and address difficulties in recognizing targets of different sizes. Secondly, we present the lite visual center (LVC) module, which effectively fuses data from different levels to give more attention to small targets. Additionally, we integrate the lite efficient layer aggregation networks (L-ELAN) into the backbone network to reduce redundant computations and enhance computational efficiency. Lastly, we use Wise-IOU to optimize the loss function definition, thereby improving the model robustness by dynamically optimizing gradient contributions from samples of varying quality. We conducted experiments on the WSODD dataset and the FIOW-Img dataset. The results on the comprehensive WSODD dataset demonstrate that STE-YOLO, when compared to YOLOv7, reduces network parameters by 14% while improving AP50 and APs scores by 2.1% and 1.6%, respectively. Furthermore, when compared to five other leading target detection algorithms, STE-YOLO demonstrates superior accuracy and efficiency.

Abstract Parkinson’s disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1β, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT–GSK-3β and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP+ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

Abstract Introduction Critical H1N1 pneumonia patients usually have one of the symptoms such as respiratory failure, septic shock, multiple organ dysfunction, or other need for intensive care management, which are associated with high risk of mortality. It is essential to differentiate the severity of H1N1 pneumonia and take corresponding target treatments. Objectives We aim to investigate the differences in clinical characteristics and chest computed tomography (CT) findings between severe and critical patients with H1N1 pneumonia. Methods A total of 27 patients diagnosed with H1N1 pneumonia from October 2018 to March 2019 were retrospectively analyzed, and the differences in clinical manifestations, laboratory tests, and chest CT findings between the severe group (15 patients) and the critical group (12 patients) were compared. Results Frequency of dyspnea at rest was higher in critical group than that in severe group (P = 0.019). The neutrophil percentage was higher (P = 0.014) and the lymphocyte percentage was lower (P = 0.025) in critical compared with severe group. Bilateral lung involvement was the predominant pattern in both severe and critical patients, whereas the number of involved lobes in critical patients was more than that in severe patients (P = 0.024). Peripheral distribution was the predominant pattern in severe patients (40%), whereas more diffuse involvement of the lungs was observed in critical patients (83.30%). Ground‐glass opacities and consolidation were the main CT findings in both groups, and prevalence of consolidation was higher in critical relative to severe group (83.30%). Conclusion Compared with severe patients, those with critical H1N1 pneumonia were more likely to present with dyspnea at rest and decreased lymphocyte percentage. Chest CT showed that diffuse bilateral involvement and higher prevalence of consolidation are associated with critical outcomes.

Genetic transformation is widely used to improve target traits and to study gene function in wheat. However, transformation efficiency depends on the physiological status of the recipient genotype and that is affected by several factors including powdery mildew (PM) infection. The widely used recipient variety Fielder is very susceptible to PM. Therefore, it would be beneficial to develop PM resistant derivatives with high regeneration ability for use in genetic transformation. In the present study PM resistant lines CB037 and Pm97033 carrying genes Pm21 and PmV, respectively, were backcrossed to Fielder with selection for PM resistance. Five lines, NT89, NT90, NT154, and WT48 with Pm21 and line FL347 with PmV were developed, identified by molecular markers and genomic in situ hybridization (GISH) or fluorescent in situ hybridization (FISH), and further subjected to detailed assessment of agronomic traits and regeneration ability following genetic transformation capacity. Lines FL347, WT48, NT89 and NT154 assessed as being equal to, or superior, to Fielder in regeneration and transformation ability are recommended as suitable materials for the replacement of Fielder for wheat gene transfer and genome editing study.

Abstract Background To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes. Methods Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used. Results In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS. Conclusions ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.

Using the aldehyde amine condensation procedure and the triphenylamine group as the skeleton structure, the new triphenylamine-aromatic aldehyde-succinylhydrazone probe molecule DHBYMH was created. A newly created acylhydrazone probe was structurally characterized by mass spectrometry (MS), NMR, and infrared spectroscopy (FTIR). Fluorescence and UV spectroscopy were used to examine DHBYMH’s sensing capabilities for metal ions. Notably, DHBYMH achieved a detection limit of 1.62 × 10−7 M by demonstrating exceptional selectivity and sensitivity towards Cu2+ ions in an optimum sample solvent system (DMSO/H2O, (v/v = 7/3); pH = 7.0; cysteine (Cys) concentration: 1 × 10−4 M). NMR titration, high-resolution mass spectrometry analysis, and DFT computation were used to clarify the response mechanism. Ultimately, predicated on DHBYMH’s reversible identification of Cu2+ ions in the presence of EDTA, a molecular logic gate was successfully designed.

Fusarium sacchari, a key pathogen of sugarcane, is responsible for the Pokkah boeng disease (PBD) in China. The 14-3-3 proteins have been implicated in critical developmental processes, including dimorphic transition, signal transduction, and carbon metabolism in various phytopathogenic fungi. However, their roles are poorly understood in F. sacchari. This study focused on the characterization of two 14-3-3 protein-encoding genes, FsBmh1 and FsBmh2, within F. sacchari. Both genes were found to be expressed during the vegetative growth stage, yet FsBmh1 was repressed at the sporulation stage in vitro. To elucidate the functions of these genes, the deletion mutants ΔFsBmh1 and ΔFsBmh2 were generated. The ΔFsBmh2 exhibited more pronounced phenotypic defects, such as impaired hyphal branching, septation, conidiation, spore germination, and colony growth, compared to the ΔFsBmh1. Notably, both knockout mutants showed a reduction in virulence, with transcriptome analysis revealing changes associated with the observed phenotypes. To further investigate the functional interplay between FsBmh1 and FsBmh2, we constructed and analyzed mutants with combined deletion and silencing (ΔFsBmh/siFsBmh) as well as overexpression (O-FsBmh). The combinations of ΔFsBmh1/siFsBmh2 or ΔFsBmh2/siFsBmh1 displayed more severe phenotypes than those with single allele deletions, suggesting a functional redundancy between the two 14-3-3 proteins. Yeast two-hybrid (Y2H) assays identified 20 proteins with pivotal roles in primary metabolism or diverse biological functions, 12 of which interacted with both FsBmh1 and FsBmh2. Three proteins were specifically associated with FsBmh1, while five interacted exclusively with FsBmh2. In summary, this research provides novel insights into the roles of FsBmh1 and FsBmh2 in F. sacchari and highlights potential targets for PBD management through the modulation of FsBmh functions.

Iodine, primarily in the form of iodide (I−), is the bioavailable form for the thyroid in the human body. Both deficiency and excess intake of iodide can lead to serious health issues, such as thyroid disease. Selecting iodide ions among anions has been a significant challenge for decades due to interference from other anions. In this study, we designed and synthesized a new pincer-type acridine–triazole fluorescent probe (probe 1) with an acridine ring as a spacer and a triazole as a linking arm attached to two naphthol groups. This probe can selectively recognize iodide ions in a mixed solvent of THF/H2O (v/v, 9/1), changing its color from colorless to light yellow, making it suitable for highly sensitive and selective colorimetric and fluorescent detection in water systems. We also synthesized another molecular tweezer-type acridine–triazole fluorescent probe (probe 2) that exhibits uniform detection characteristics for iodide ions in the acetonitrile system. Interestingly, compared to probe 2, probe 1 can be detected by the naked eye due to its circulation effect, providing a simple method for iodine detection. The detection limit of probe 1 is determined to be 10−8 mol·L−1 by spectrometric titration and isothermal titration calorimetry measurements. The binding stoichiometry between probe 1 and iodide ions is calculated to be 1:1 by these methods, and the binding constant is 2 × 105 mol·L−1.

Series superconducting Josephson junctions (JJs), as terahertz (THz) mixers, have attracted increasing attentions due to their advantages in solving the saturation problem of superconducting mixers, achieving higher mixing harmonics and higher sensitivity in THz band. However, the normal-state resistances of the series JJs are so low that there exists an impedance mismatch between the coupled antenna and the JJs. In this paper, a meander embedding travelling-wave bowtie antenna is proposed for a series of bicrystal JJs. With this antenna, not only the problem of impedance mismatch can be solved, but also more series JJs can be inserted into the antenna. Five and even seven series JJs in the meander match the proposed antenna well. Furthermore, combined current distribution, far-field radiation patterns and parameter study are investigated in the numerical simulation to analyze this antenna.

Abstract Maxillofacial hard tissue defects caused by trauma or infection often affect craniofacial function. Taking the natural hard tissue structure as a template, constructing an engineered tissue repair module is an important scheme to realize the functional regeneration and repair of maxillofacial hard tissue. Here, inspired by the biomineralization process, we constructed a composite mineral matrix hydrogel PAA-CMC-TDM containing amorphous calcium phosphates (ACPs), polyacrylic acid (PAA), carboxymethyl chitosan (CMC) and dentin matrix (TDM). The dynamic network composed of Ca 2+ ·COO − coordination and ACPs made the hydrogel loaded with TDM, and exhibited self-repairing ability and injectability. The mechanical properties of PAA-CMC-TDM can be regulated, but the functional activity of TDM remains unaffected. Cytological studies and animal models of hard tissue defects show that the hydrogel can promote the odontogenesis or osteogenic differentiation of mesenchymal stem cells, adapt to irregular hard tissue defects, and promote in situ regeneration of defective tooth and bone tissues. In summary, this paper shows that the injectable TDM hydrogel based on biomimetic mineralization theory can induce hard tissue formation and promote dentin/bone regeneration.

Abstract Background Brown adipose tissue (BAT) is considered as a primary location of adaptive thermogenesis and the thermogenic activities of brown adipocytes are also connected to generating heat and counteracting obesity. Recent studies revealed that BAT could secrete certain batokines-like factors especially small extracellular vesicles (sEVs), which contributed to the systemic consequences of BAT activities. As a newly emerging class of mediators, some long non-coding RNAs (lncRNAs) have exhibited metabolic regulatory effects in adipocyte development. However, besides the well-studied lncRNAs, the lncRNAs carried by sEVs derived from brown adipose tissue (sEV-BAT) have not been identified yet. Results In this study, we demonstrated that sEV-BAT could induce beige adipocyte differentiation both in ASCs and 3T3-L1 cells, while sEV-WAT had no corresponding effects. The lncRNA microarray assay on sEV-WAT and sEV-BAT revealed a total of 563 types of known lncRNAs were identified to be differentially expressed, among which 232 lncRNAs were upregulated and 331 lncRNAs were downregulated in sEV-BAT. Three novel candidates (AK029592, humanlincRNA1030 and ENSMUST00000152284) were selected for further validation. LncRNA–mRNA network analysis revealed candidate lncRNAs were largely embedded in cellular metabolic pathways. During adipogenic and thermogenic phenotype differentiation in ASCs and 3T3-L1 cells, only the expressions of AK029592 were upregulated. The three lncRNAs were all relatively enriched in brown adipose tissues and brown adipocytes. In different adipocytes, sEV and adipose tissue, the expression of AK029592 and ENSMUST00000152284 were remarkably decreased in obese mice compared to lean mice, while obesity state could not change the expression of humanlincRNA1030. Conclusion Collectively, our profiling study provided a comprehensive catalog for the study of lncRNAs specifically carried by sEV-BAT and indicated the potential regulatory role of certain sEV-BAT lncRNAs in thermogenesis.

AimsWe aimed to explore the metabolic features of lean nonalcoholic fatty liver disease (Lean-NAFLD) and its association with the risk of incident type 2 diabetes in young and middle-aged people.MethodsWe conducted a retrospective cohort study of 3001 participants who were enrolled in a health check-up program from January 2018 to December 2020 in the Health Management Center of Karamay People’s Hospital. The age, sex, height, weight, body mass index (BMI), blood pressure, waist circumference (WC), fasting plasma glucose (FPG), lipid profiles, serum uric acid and alanine aminotransferase (ALT) of the subjects were collected. The cutoff point of BMI for lean nonalcoholic fatty liver disease is 0.05) and 4.20 (95% CI 1.44-12.22, p

Background: The regenerative capabilities of derivatives derived from the fat layer of lipoaspirate have been demonstrated. However, the large volume of lipoaspirate fluid has not attracted extensive attention in clinical applications. In this study, we aimed to isolate the factors and extracellular vesicles from human lipoaspirate fluid and evaluate their potential therapeutic efficacy.Methods: Lipoaspirate fluid derived factors and extracellular vesicles (LF-FVs) were prepared from human lipoaspirate and characterized by nanoparticle tracking analysis, size-exclusion chromatography and adipokine antibody arrays. The therapeutic potential of LF-FVs was evaluated on fibroblasts in vitro and rat burn model in vivo. Wound healing process was recorded on days 2, 4, 8, 10, 12 and 16 post-treatment. The scar formation was analyzed by histology, immunofluorescent staining and scar-related gene expression at day 35 post-treatment.Results: The results of nanoparticle tracking analysis and size-exclusion chromatography indicated that LF-FVs were enriched with proteins and extracellular vesicles. Specific adipokines (adiponectin and IGF-1) were detected in LF-FVs. In vitro, LF-FVs augmented the proliferation and migration of fibroblasts in a dose-dependent manner. In vivo, the results showed that LF-FVs significantly accelerated burn wound healing. Moreover, LF-FVs improved the quality of wound healing, including regenerating cutaneous appendages (hair follicles and sebaceous glands) and decreasing scar formation in the healed skin.Conclusion: LF-FVs were successfully prepared from lipoaspirate liquid, which were cell-free and enriched with extracellular vesicles. Additionally, they were found to improve wound healing in a rat burn model, suggesting that LF-FVs could be potentially used for wound regeneration in clinical settings.

The ε4 allele of the lipoprotein E gene (APOE4) is the strongest genetic risk factor associated with sporadic Alzheimer's disease (sAD). While the neuronal cell type-specific function of APOE4 in connection with AD pathology remains understudied. Therefore, we generated an induced pluripotent stem cells (iPSCs) line from a 77-year-old female donor with ApoE4 genetic background. We reprogrammed peripheral blood mononuclear cells (PBMCs) with non-integrative Sendai viral vectors containing reprogramming factors. Established iPSCs showed the capability of pluripotency, three-germ differentiation in vitro with normal karyotype. Hence, the generated iPSC could be a powerful tool to conduct further studies of AD mechanisms.

Extreme climate events such as storms and severe droughts are becoming more frequent under the warming climate. In the tropics, excess rainfall carried by hurricanes causes massive flooding and threatens ecosystems and human society. We assessed recent major floodings on the tropical island of Puerto Rico after Hurricane Maria in 2017 and Hurricane Fiona in 2022, both of which cost billions of dollars damages to the island. We analyzed the Sentinel-1 synthetic aperture radar (SAR) images right after the hurricanes and detected surface inundation extent by applying a random forest classifier. We further explored hurricane rainfall patterns, flow accumulation, and other possible drivers of surface inundation at watershed scale and discussed the limitations. An independent validation dataset on flooding derived from high-resolution aerial images indicated a high classification accuracy with a Kappa statistic of 0.83. The total detected surface inundation amounted to 10,307 ha after Hurricane Maria and 7949 ha after Hurricane Fiona for areas with SAR images available. The inundation patterns are differentiated by the hurricane paths and associated rainfall patterns. We found that flow accumulation estimated from the interpolated Fiona rainfall highly correlated with the ground-observed stream discharges, with a Pearson’s correlation coefficient of 0.98. The detected inundation extent was found to depend strongly on hurricane rainfall and topography in lowlands within watersheds. Normal climate, which connects to mean soil moisture, also contributed to the differentiated flooding extent among watersheds. The higher the accumulated Fiona rain and the lower the mean elevation in the flat lowlands, the larger the detected surface flooding extent at the watershed scale. Additionally, the drier the climate, which might indicate drier soils, the smaller the surface flooding areas. The approach used in this study is limited by the penetration capability of C-band SAR; further application of L-band images would expand the detection to flooding under dense vegetation. Detecting flooding by applying machine learning techniques to SAR satellite images provides an effective, efficient, and reliable approach to flood assessment in coastal regions on a large scale, hence helping to guide emergency responses and policy making and to mitigate flooding disasters.

Abstract Electrophysiological monitoring under strenuous exercise by using stretchable dry electrodes is vital for healthcare monitoring, prosthetic control, human−machine interfaces and other biomedical applications. However, the existing dry electrodes are not applicable to the strenuous exercise situation that always involves both fast moving and profuse sweating. Herein, we present a nano-thick porous stretchable dry electrode system with high stretchability and water permeability. The system attaches conformably to the skin and stretches with it under Van der Waals forces even at sweating conditions, allowing the detection of electromyogram when moving with an acceleration of 10 g at a sweating rate of 2.8 mg cm−2 min−1. It is also capable of acquiring electrocardiogram and electroencephalogram signals. The strategy proposed would enable the biomedical studies and related applications with the requirement of stably recording electrophysiological signals under strenuous exercise scenarios.

Abstract The endocannabinoid anandamide (AEA) produces antinociceptive effects by activating cannabinoid receptor 1 (CB1). However, AEA also serves as an agonist at transient receptor potential vanilloid receptor 1 (TRPV1) in nociceptive sensory neurons, which may exacerbate pain. This potential functional duality is highlighted by the failure of an inhibitor of the AEA catabolic enzyme fatty acid amide hydrolase (FAAH) to afford pain relief in a clinical trial. Consequently, it remains to be determined whether elevating AEA levels in nociceptors leads to antinociceptive or pro-nociceptive effects. Fatty acid binding protein 5 (FABP5) is an intracellular carrier that mediates AEA transport to FAAH for inactivation. Leveraging the abundant expression of FABP5 in TRPV1+ nociceptors, we employed a conditional knockout strategy to demonstrate that FABP5 deletion in nociceptors augments AEA levels, resulting in the emergence of antinociceptive effects mediated by CB1. Mechanistically, FABP5 deletion suppresses inflammation- and nerve growth factor-mediated TRPV1 sensitization via CB1, an effect mediated by calcineurin. Unexpectedly, inhibition of FAAH failed to blunt TRPV1 sensitization, uncovering functionally distinct outputs resulting from FABP5 and FAAH inhibition. Collectively, our results demonstrate that FABP5 serves a key role in governing endocannabinoid signaling in nociceptors to disrupt TRPV1 sensitization and pain, and position FABP5 as a therapeutic target for the development of analgesics.

Fluorescence based corrosion detection has been proposed as a prospective monitoring method for the initial corrosion of metals due to its high sensitivity, non-destructive, in situ and real-time detection. This paper provides a comprehensive and updated review on the fluorescence based corrosion detection of metals. The principles of fluorescence based corrosion detection are introduced according to the corrosion processes of metals. Fluorescent indicators in corrosion detection are classified into pH and metal ion sensitive indicators, which show fluorescence response either by the pH variation or the presence of metallic cations as an early warning for corrosion initiation. The addition manners of fluorescent indicators and influence factors of fluorescence detection sensitivity are summarized. Finally, some critical prospects of fluorescence based corrosion detection are proposed.

Objective To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. Methods The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. Results From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P

Alniaria alnifolia (Siebold and Zucc.) Rushforth, 2018 (alternative name: Sorbus alnifolia) belongs to the genus Alniaria of the family Rosaceae and is widely distributed in northern China, Korea, and Japan. It is an essential resource used in the construction, pharmaceuticals, and food industries. It is also used to treat various diseases, such as fever, hyperglycemia, rash, asthma, bronchitis, constipation, leprosy, anemia, and other skin ailments. In this study, we sequenced a sample of A. alnifolia and determined its complete chloroplast genome. The chloroplast genome of A. alnifolia has a circular structure with a length of 159,855 bp, which includes a small single-copy region (19,409 bp), a large single-copy region (87,628 bp), and two inverted repeats (26,409 bp). The sequence had 130 genes, including 85 protein-coding genes, eight rRNA genes, and 37 tRNA genes, and the overall GC content was 36.6%. The genes trnK-UUU, rps16, trnG-UCC, atpF, rpoC1, trnL-UAA, trnV-UAC, petB, petD, rpl16, rpl2, ndhB, trnI-GAU, trnA-UGC, and ndhA contained one intron; genes clpP and ycf3 contained two introns. Phylogenetic results showed that A. alnifolia had the closest relationship with Sorbus folgneri (MK161058).

Abstract Background Cell-free therapy has been inspired as a promising approach to overcome the limitations of traditional stem cell therapy. However, the therapeutic effect between extracellular vesicles and conditioned medium with the same source had not been compared. Our previous studies have shown that both the conditioned medium of adipose tissue (adipose tissue extract, ATE) and its further purification product small extracellular vesicles (sEV-AT) contributed to adipose tissue regeneration. In this study, we aimed to compare the ATE and sEV-AT in composition, inductivity on cells and de novo adipose regenerative potential. Methods The characteristics of sEV-AT and ATE were compared through protein and particle yield, particle size distribution and composition. The inductivity of sEV-AT and ATE on cells were compared through co-culture of sEV-AT or ATE with ASC, HUVEC and RAW264.7 in vitro. The capacity of promoting de novo adipogenesis was compared by implanting the silicone tube containing sEV-AT or ATE subcutaneously in vivo. Results More particles and concentrated particle size distribution were detected in sEV-AT. In turn, more soluble factors and multiple peaks in particle size distribution were detected in ATE. In 1662 common proteins of sEV-AT and ATE, there were 984 (59.2%) proteins enriched twice more in sEV-AT than in ATE. With the prerequisite of equivalent protein concentration, sEV-AT outperformed ATE in promoting proliferation, migration and regeneration potential of cells those contributing adipose tissue regeneration in vitro. Furthermore, sEV-AT expedited the de novo adipose tissue regeneration and angiogenesis at the early stage than ATE in vivo, but sEV-AT and ATE group formed similar neoadipose tissue and new vessels at week 12. Conclusions Our results provided a direct comparison between EV and conditioned medium as cell-free therapeutic strategy. Both sEV and ATE had specific biological signature to facilitate tissue repair. Considering the convenience of extraction and acceptable effect, ATE represented a feasible product of cell-free therapy, providing another option for different situations in clinical application. Furthermore, the complex contents of both sEV-AT and ATE should be studied comprehensively to avoid possible negative effects and to ensure sufficient safety for clinical applications.

Abstract Background Browning of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Although small extracellular vesicles (sEVs) released from adipose tissue (sEVs-AT) have emerged as novel player that regulate systemic metabolism by connecting different organs, the role of specific contents in sEVs-AT played in WAT browning has not been clarified. Results We revealed Nucleophosmin3 (NPM3), which was mainly transferred by sEVs derived from brown adipose tissue (sEVs-BAT), was served as a batokine that could induce WAT browning by regulating the stability of PRDM16 mRNA. sEVs-BAT enhanced the expressions of browning related genes in 3T3-L1 preadipocytes and WAT while knocking down of NPM3 in BAT impaired sEVs-BAT mediated WAT browning and weight loss in obesity. Conclusion These data provided new insight into the role of NPM3 in regulating the browning of WAT. Our study indicated that a supplement of sEVs-BAT might represent a promising therapeutic strategy to promote thermogenesis and energy expenditure in the future. Graphical Abstract

Abstract Coloured point cloud (CPC) is one of the important representations of three‐dimensional objects, which has been used in many fields. CPC may encounter geometric and colour distortion during its compression, simplification or other processing. Thus, the objective visual quality assessment of CPC is one of the urgent issues to be resolved in the CPC's applications. Aiming at this problem, this paper proposes a new full‐reference visual quality assessment metric for CPC based on geometric segmentation and colour transformation (CPC‐GSCT), which analyzes geometric distortion and colour distortion of CPC. First, considering the visual masking effect of CPC's geometric information, CPC is segmented into different regions and distributed with different weights to describe the influence of visual masking effect in CPC quality assessment. At the same time, a geometric combination feature vector is defined and extracted for measuring the CPC's geometric distortion. Then, considering the colour perception of human eyes, a colour combination feature vector is extracted to measure the CPC's colour distortion in HSV colour space. Finally, all the extracted geometric and colour features are constituted as a feature vector to predict the quality of CPC. Experimental results on three databases (IRPC, SJTU‐PCQA and CPCD2.0) show that the proposed CPC‐GSCT metric can achieve better performance in predicting the visual quality of CPC than relevant existing methods.

In this study, a functional segmentation method for the design of adiabatic devices is presented. This method can be applied to calculate the compact adiabatic waveguide shapes for adiabatic taper waveguides and adiabatic mode converters. We introduce two algorithms, namely the quadratic function segmentation design for the adiabatic taper waveguide and the cubic function segmentation design for the adiabatic mode coupler. The design shows that for each segment, there is no need for separate simulations to obtain the length of each segment, and only the length of each segment can be determined by equations. This approach is much less cumbersome than other numerical design methods for adiabatic devices. The proposed functional segmentation design requires only a device length of 36 μm to achieve 95% power transfer efficiency, while a traditional linear-shape connection requires a device length of 54 μm to achieve the same power transfer efficiency. Therefore, the device designed by the function segmentation method has better compactness compared to the conventional linear-shape connection design of adiabatic devices.

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Abstract Background Ketogenic diet (KD) therapy is one of the main treatments for drug-resistant epilepsy. However, the KD therapy has been applied in only a small number of infantile spasm cases. In this large multicenter study, we investigated the efficacy of KD therapy in the treatment of infantile spasms. Methods In this retrospective, multicenter cohort study, clinical data from main epilepsy centers were analyzed. Patients were classified into different groups according to age, type of drug and whether glucocorticoid was used before initiation of KD. Results From October 2014 to March 2020, 481 patients (308 males and 173 females) with infantile spasms were treated with the KD therapy. The age of the patients ranged from 2 months to 20 years, with a mean age of 1 year and 10 months. The number of anti-seizure medications (ASMs) used before KD initiation ranged 0–6, with a median of 3. In different time from initiation(1, 3, 6, and 12 months), the rates of seizure freedom after KD were 6.9, 11.6, 16.0 and 16.8%, respectively (χ 2 = 27.1772, P 0.05). Two hundred and eighteen patients (45.3%) failed to respond to corticotropin or glucocorticoid before initiation. There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (χ 2 = 0.8613, P = 0.8348). The rate of adverse events of KD in 1, 3, 6, and 12 months after KD initiation were 22.3, 21.7, 16.8 and 6.9%, respectively. The adverse events mainly occurred during the first 3 months of KD, and the main adverse events were gastrointestinal disturbance and constipation. Conclusion The efficacy of the KD treatment for infantile spasms was not affected by age, medication, and glucocorticoid use before initiation. KD is one of the effective treatments for infantile spasms. Trial registration ChiCTR-IIR-16008342. Registered on 22 April, 2016 - Retrospectively registered, https://www.chictr.org.cn .

Abstract Background Despite the consistency of patient age, disease stage and treatment options, the prognosis of different high-grade serous ovarian carcinoma (HGSOC) patients is different. Here, we sought to measure predictive biomarkers for distinct responses to platinum-based chemotherapy and immunotherapy benefits. Methods Sixteen HGSOC patients receiving debulking surgery and adjuvant first-line combination chemotherapy at Peking Union Medical College Hospital (PUMCH) were enrolled. Whole exome sequencing (WES) and RNA-seq were performed on tumor and normal tissues of these patients. Results The tumor mutational burden (TMB) and intratumoral heterogeneity (ITH) of the platinum-resistant group were significantly higher than those of the platinum-sensitive group (P=0.0321 and P=0.0452, respectively). TMB, neoantigen and ITH had certain predictive value according to the area under the receiver operating characteristic (ROC) curve (AUC 0.7778 for TMB, 0.7619 for neoantigen, 0.7778 for ITH). The infiltration of other immune cells in tumor tissues was different between the two groups, but the difference was not significant. Univariate Cox proportional hazard analysis revealed poorer progression-free survival (PFS) for those patients who carried a higher number of neoantigens (P =0.0069), higher TMB (P =0.0083), and higher ITH (P =0.0249). Further Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis indicated the Differentially expressed genes (DEGs) in platinum-resistant and platinum-sensitive patients were mainly enriched in the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway and focal adhesion pathway, which are associated with platinum resistance. Conclusions Higher TMB, neoantigen and ITH may account for the worse prognosis of patients with platinum-based chemotherapy and higher TMB was observed in the platinum-resistant group, which could make the patients in the platinum-resistant group to be the better candidates for immunotherapy.

Botrytis cinerea causing tomato gray mold is a major cause of economic loss in tomato production. It is urgent and necessary to seek an effective and environmentally friendly control strategy to control tomato grey mold disease. In this study, Bacillus velezensis FX-6 isolated from the rhizosphere of plants displayed significant inhibitory ability against B. cinerea and could promote tomato plant growth. FX-6 could effectively inhibit the growth of Botrytis cinerea mycelium in vitro and in vivo, and the inhibitory rate in vitro could reach 78.63%. According to morphological observations and phylogenetic trees based on sequences of the 16S rDNA and gyrA (DNA gyrase subunit A) genes, the strain FX-6 was identified as Bacillus velezensis. In addition, B. velezensis FX-6 showed antagonistic activity against seven phytopathogens, this indicated that FX-6 had broad-spectrum biocontrol activity. We also found that FX-6 fermentation broth had the strongest antagonistic activity against B. cinerea when the culture time was 72 hours, and the inhibition rate was 76.27%. The growth promotion test revealed that strain FX-6 significantly promoted tomato seed germination and seedling growth. Further deeply study on growth-promoting mechanism indicated that the FX-6 produced IAA and siderophore, and had ACC deaminase activity. The trait of significant biological control activity and growth promoting effect on tomato imply that B. velezensis FX-6 has the potential to be used as a biocontrol agent for tomato gray mold management.

ObjectiveDespite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet.MethodsPatients suffering from infantile spasms who had at least 2 years of medical records in the electronic medical record system between January 2014 and August 2022 were included in this study. Patient information was retrospectively reviewed. All patients had received ketogenic diet therapy (mainly classical ketogenic diet therapy). The ketogenic diet therapy was combined with ASMs not used as first-line therapies. The primary endpoint outcome measure was the number of patients with seizure freedom. The secondary measures included the duration of ketogenic diet therapy, choice of ASMs, and patient development at the last visit.ResultsA total of 177 patients with infantile spasms were included, and 152 (86%) of them had seizure freedom. The median duration from the first to the last hospital visit was 53.27 months, and the number of visits was 47.00. The median age at the initial hospital visit was 8.00 months, and the median age at initiation of the ketogenic diet was 17.73 months. At the last visit, the proportions of patients with neurodevelopmental delay, developmental epileptic encephalopathy, drug-resistant epilepsy, and generalized seizures increased significantly. The frequently used ASMs were topiramate, valproic acid, levetiracetam, nitrazepam, and vitamin B6 injection, while the recommended first-line drugs corticotropin and vigabatrin were rarely selected. The study duration of 9.5 years was divided into three periods but the prescription of ASMs did not change significantly between these periods.ConclusionsAlthough the seizure freedom rate was high with ketogenic diet therapy combined with non-standard ASMs, the patients had a significant neurodevelopmental delay at the last visit, which was, however, similar to that of standard treatment. To improve the outcomes of infantile spasms, multicenter clinical trials of the ketogenic diet as a first-line treatment in combination with non-standard ASMs are needed.

Adipose tissue, which is considered an energy storage and active endocrine organ, produces and secretes a large amount of adipokines to regulate distant targets through blood circulation, especially extracellular vesicles (EVs). As cell-derived, membranous nanoparticles, EVs have recently garnered great attention as novel mediators in establishing intercellular communications as well as in accelerating interorgan crosstalk. Studies have revealed that the RNAs, including coding RNAs (messenger RNAs) and noncoding RNAs (long noncoding RNAs, microRNAs, and circular RNAs) are key bioactive cargoes of EV functions in various pathophysiological processes, such as cell differentiation, metabolic homeostasis, immune signal transduction, and cancer. Moreover, certain EV-contained RNAs have gradually been recognized as novel biomarkers, prognostic indicators, or even therapeutic nanodrugs of diseases. Therefore, in this review, we comprehensively summarize different classes of RNAs presented in adipose-derived EVs and discuss their therapeutic potential according to the latest research progress to provide valuable knowledge in this area.

In this paper, an adiabatic operation slope-loss algorithm (AO-SLA) is developed for designing efficient adiabatic waveguide tapers. The algorithm can compute the efficient adiabatic guided-wave shape of the waveguide taper. A well-studied case of an adiabatic waveguide taper is used to show how it can readily generate a guided-wave shape that gives the same mode-connection power transfer with a much shorter length compared with the linear shape. In the waveguide taper design, it is shown that the device efficiency designed with AO-SLA is better than that based on the parabolic case and the SLA case, and the adiabatic taper designed can give a broad operating bandwidth. Moreover, the adiabatic condition α for AO-SLA can be very large.

Abstract Long noncoding RNAs are a group of more than 200 nt, nonprotein coding RNAs, some of which are dysregulated in many pathophysiological processes including endometriosis. This study aims to clarify the roles of dysregulated growth arrest‐specific 5 (GAS5) in patients with endometriosis, and unveil the underlying mechanisms. We obtained endometrium samples from 37 patients with endometriosis and 23 controls without endometriosis. Primary endometrial stromal cells (ESCs) and endothelial cells were separated from the endometrium. Levels of GAS5 were quantified using quantitative real‐time polymerase chain reaction, and levels of p27, cleaved caspase‐3, cleaved poly (ADP‐Ribose) polymerase 1, vascular endothelial growth factor A, tissue inhibitor of metalloproteinases 3 (TIMP3), and trypsin‐modified soy protein 10 were assessed by immunoblotting. Cell viability was examined using MTT assays, and the cell cycle and apoptosis were analyzed by flow cytometry. Endothelial cell tube formation capacity was assayed in vitro. GAS5 and p27 levels were found lower in the endometrium samples from patients with endometriosis. Primary ESCs from patients with endometriosis had increased viability, reduced apoptosis, and a relatively uncontrolled cell cycle. Gain‐ and loss‐of‐function studies confirmed that GAS5 regulated p27 expression in ESCs. Furthermore, GAS5 level was relatively low in primary endothelial cells from patients with endometriosis and GAS5 acted as an angiogenesis inhibitor by regulating the miR‐181c‐TIMP3 axis. Thus, lower GAS5 level in endometrium might be related to endometriosis by regulating cell proliferation, apoptosis, cell cycle, and angiogenesis.