Association of Graft Maturity on MRI With Return to Sports at 9 Months After Primary Single-Bundle ACL Reconstruction With Autologous Hamstring Graft.

Background: The relationship between graft maturity on magnetic resonance imaging (MRI) and return to sports (RTS) after anterior cruciate ligament (ACL) reconstruction is unclear. Purpose: To compare signal-to-noise quotient (SNQ) values and ACL graft T2* (gradient echo) values between patients who did RTS and those who did not RTS (NRTS) after ACL reconstruction and to evaluate the predictive value of T2* mapping for RTS after ACL reconstruction. Study Design: Case-control study; Level of evidence, 3. Methods: At a minimum of 9 months after arthroscopic single-bundle ACL reconstruction with autologous hamstring tendon graft, 82 patients underwent RTS assessment as well as MRI evaluation. The patients were classified into RTS (n = 53) and NRTS (n = 29) groups based on the results of the assessment. The SNQ values in the proximal, middle, and distal regions of the graft and the T2* values of the graft were measured on MRI. The correlation between T2* values and RTS was assessed using Spearman correlation analysis. Receiver operating characteristic curves were constructed to compare the diagnostic performance, and the optimal T2* cutoff value for detecting RTS was determined based on the maximum Youden index. Results: At 9 months after ACL reconstruction, the proximal, middle, and mean SNQ values in the RTS group were significantly lower than those in the NRTS group (proximal: 17.15 ± 4.85 vs 19.55 ± 5.05, P = .038; middle: 13.45 ± 5.15 vs. 17.75 ± 5.75, P = .001; mean: 12.37 ± 2.74 vs 15.07 ± 3.32, P < .001). The T2* values were lower in the RTS group (14.92 ± 2.28 vs 17.69 ± 2.48; P < .001) and were correlated with RTS (r = -0.41; P = .02). The area under the curve of T2* was 0.79 (95% CI, 0.75-0.83), and the optimal cutoff value for T2* was 16.65, with a sensitivity and specificity for predicting failure to RTS of 67.9% and 88.2%, respectively. Conclusion: Study findings indicated that the SNQs (mean, proximal, and middle) and the T2* values of the graft in the RTS group were significantly lower than those in NRTS group. A T2* value of 16.65 was calculated to predict patients who failed RTS tests with a sensitivity of 67.9% and specificity of 88.2%.

PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating ß-amyloid and targeting the ERK pathway.

BACKGROUND: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. PURPOSE: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. METHODS: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. RESULTS: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of ß-amyloid, reduced the content and abnormal accumulation of the toxic Aß1-42 protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. CONCLUSION: PRG promoted ß-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.

Mitochondrial regulation of diabetic endothelial dysfunction: Pathophysiological links.

Micro- and macrovascular complications frequently occur in patients with diabetes, with endothelial dysfunction playing a key role in the development and progression of the complications. For the early diagnosis and optimal treatment of vascular complications associated with diabetes, it is imperative to comprehend the cellular and molecular mechanisms governing the function of diabetic endothelial cells. Mitochondria function as crucial sensors of environmental and cellular stress regulating endothelial cell viability, structural integrity and function. Impaired mitochondrial quality control mechanisms and mitochondrial dysfunction are the main features of endothelial damage. Hence, targeted mitochondrial therapy is considered promising novel therapeutic options in vascular complications of diabetes. In this review, we focus on the mitochondrial functions in the vascular endothelial cells and the pathophysiological role of mitochondria in diabetic endothelial dysfunction, aiming to provide a reference for related drug development and clinical diagnosis and treatment.

Investigating the impact of HMI on drivers' merging performance in intelligent connected vehicle environment.

Intelligent Connected Vehicle (ICV) is considered one of the most promising active safety technologies to address current transportation challenges. Human-Machine Interface (HMI) plays a vital role in enhancing user driving experience with ICV technology. However, in an ICV environment, drivers may exhibit excessive reliance on HMI, resulting in diminished proactive observation and analysis of the road environment, and subsequently leading to a potential decrease in drivers' situational awareness. This reduced situational awareness may consequently lead to a decline in their overall engagement in driving tasks. Therefore, to comprehensively investigate the impact of HMI on driver performance in various ICV environments, this study incorporates three distinct HMI systems: Control group, Warning group, and Guidance group. The Control group provides basic information, the Warning group adds front vehicle icon and real-time headway information, while the Guidance group further includes speed and voice guidance features. Additionally, the study considers three types of mainline vehicle gaps, namely, 30 m, 20 m, and 15 m. Through our self-developed ICV testing platform, we conducted driving simulation experiments on 43 participants in a freeway interchange merging area. The findings reveal that, drivers in the Guidance group exhibited explicit acceleration while driving on the ramp. Drivers in the Guidance and Warning groups demonstrated smoother speed change trends and lower mean longitudinal acceleration upon entering the acceleration lane compared to the Control group, indicating a preference for more cautious driving strategies. During the pre-merging section, drivers in the Warning group demonstrated a more cautious and smooth longitudinal acceleration. The Guidance group's HMI system assisted drivers in better speed control during the post-merging section. Differences in mainline vehicle gaps did not significantly impact the merging positions of participants across the three HMI groups. Drivers in the Guidance group merged closest to the left side of the taper section, while the Control group merged farthest. The research findings offer valuable insights for developing dynamic human-machine interfaces tailored to specific driving scenarios in the environment of ICVs. Future research should investigate the effects of various HMIs on driver safety, workload, energy efficiency, and overall driving experience. Conducting real-world tests will further validate the findings obtained from driving simulators.

Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Aß damage and targeting the ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect ß-amyloid (Aß) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Aß deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Aß damage and targeting the ERK pathway.

Recent Progress on Durable Metal-N-C Catalysts for Proton Exchange Membrane Fuel Cells.

It is essential for the widespread application of proton exchange membrane fuel cells (PEMFCs) to investigate low-cost, extremely active, and long-lasting oxygen reduction catalysts. Initial performance of PGM-free metal-nitrogen-carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) has advanced significantly, particularly for Fe-N-C-based catalysts. However, the insufficient stability of M-N-C catalysts still impedes their use in practical fuel cells. In this review, we focus on the understanding of the structure-stability relationship of M-N-C ORR catalysts and summarize valuable guidance for the rational design of durable M-N-C catalysts. In the first section of this review, we discuss the inherent degrading mechanisms of M-N-C catalysts, such as carbon corrosion, demetallation, H2 O2 attack, etc. As we gain a thorough comprehension of these deterioration mechanisms, we shift our attention to the investigation of strategies that can mitigate catalyst deterioration and increase its stability. These strategies include enhancing the anti-oxidation of carbon, fortifying M-N bonds, and maximizing the effectiveness of free radical scavengers. This review offers a prospective view on the enhancement of the stability of non-noble metal catalysts.

Novel Circular RNA CircUBAP2 Drives Tumor Progression by Regulating the miR-143/TFAP2B Axis in Prostate Cancer.

BACKGROUND: More and more investigations reveal that circular RNAs (circRNAs) are involved in cancer progression. CircRNA UBAP2 was closely related to prostate cancer. However, the biological function and specifical mechanism of circUBAP2 are still poorly discovered in prostate cancer (PCa). OBJECTIVES: This study aims to explore the biological function and mechanism of circUBAP2 in PCa. METHODS: The levels of mRNA and proteins were assessed by qRT-PCR assay and Western blot, respectively. Cell growth, migration, and invasion ability were measured using CCK-8 assay and Transwell assay. Apoptosis was assessed using flow cytometry. The interactions between circUBAP2, miR-143, and TFAP2B were determined by luciferase report assay. The tumor growth was determined by in vivo tumor formation assay. The tumor morphology was assessed using H&E staining assay, and immunohistochemistry assay was conducted to assess the level of KI67. RESULTS: We found circUBAP2 and TFAP2B were notably elevated, while miR-143 was largely attenuated in prostate cancer cells and tissues. CircUBAP2 was found to affect cell viability, metastasis and EMT, while attenuating the apoptosis rate of prostate cancer cells. CircUBAP2 directly targeted miR-143, and miR-143 inhibitor could reverse the effects that circUBAP2 interference-induced in prostate cancer cells. TFAP2B is directly bound to miR-143, and overexpression of TFAP2B could attenuate the influences that miR-143-induced in prostate cancer cells. CONCLUSION: CircUBAP2 promoted prostate cancer progression via miR-143/TFAP2B axis.

Orthokeratology combined with spectacles in moderate to high myopia adolescents.

PURPOSE: Wearing ortho-k lenses overnight may not fully correct their daytime refractory errors of adolescents with moderate to high myopia. There are three common ways to deal with the daytime residual refractive error (RRE): 1) wearing spectacles to correct the RRE; 2) wear ortho-k lenses during the daytime instead of overnight.; 3) not correcting the residual refractive error. According to previous laboratory studies, myopic peripheral refraction is associated with better myopic control. This study had two aims:1) to compare relative peripheral refractive error (RPRE) among these ways after one-month stabilization; 2) to assess the axial length changes over 2 years of ortho-k lens overnight wear combined with spectacle glasses. METHODS: This was a prospective, non-controlled, non-randomized, observational study in which a total of 27 subjects (20 females, 7 males, mean age 12.48 ± 2.23Y) with spherical equivalent refractive error from -5.00 to -8.25D were enrolled. All participants in the study wore orthokeratology (ortho-k) lenses overnight for a minimum of one month. Subsequently, their peripheral refractive error (PRE) was assessed using an open-field autorefractor. During the assessment, the participants underwent three conditions in a random order in a same morning: 1) unaided eye after orthokeratology (referred to as the Unaided-eye condition), 2) wearing glasses to correct any remaining refractive errors after orthokeratology (referred to as the Spec-RE condition), and 3) wearing ortho-k lenses during the daytime (referred to as the Continuous OK wear condition). After testing, all subjects were instructed to wear ortho-k lenses overnight and glasses during the daytime to correct their RRE for the next 2 years, during which time the progression of their axial length was followed up. RESULTS: 1) RPRE in either Unaided-eye or Spec-RE condition subjects were significantly more myopic than those in the Continuous OK wear condition. 2) No difference in RPRE was seen between Unaided-eye and Spec-RE conditions. 3) Axial length growth was 0.05 ± 0.20 mm and 0.17 ± 0.32 mm (mean ± standard deviation) at 1-year and 2-year follow-ups after the initial visit, respectively, which were comparable to mild myopia patients after orthokeratology. 4) After orthokeratology, axial length change had negative correlation with the initial age (p = 0.001, r = -0.616) and residual diopter (p = 0.022). CONCLUSIONS: For myopes above refraction < -5.00D, wearing Ortho-k lenses overnight and glasses to correct the RRE in the daytime is recommended to ensure good visual quality and have more myopic RPRE for potential myopia control.

Electrochemical Synthesis of Copper Mesh-Supported Thermo-Catalysts.

Metallic substrates, widely studied in the context of monolithic catalysts, offer inherent advantages in heterogeneous catalysis due to their exceptional thermal conductivity and mechanical properties. However, synthesizing stable monolithic catalysts with metallic substrates in a well-controlled manner remains a significant challenge. Here, this work introduces a simple, cost-efficient method to fabricate robust Cu mesh-supported thermo-catalysts using a modified cycling chronopotentiometry approach, where the Cu mesh serves as a donor of Cu ions. In this method, the Cu mesh surface generates two distinct layers of CuO and Cu2 O. In this context, CuO acts as the active phase, accounting for the high CO oxidation activity of Cu mesh catalysts with T90 ≈ 120 °C. Additionally, these catalysts exhibit considerable potential in electrocatalysis, showcasing significant research and application value.

Vacancy-Mediated Control of Local Electronic Structure for High-Efficiency Electrocatalytic Conversion of N2 to NH3.

Ambient electrocatalytic nitrogen (N2 ) reduction has gained significant recognition as a potential substitute for producing ammonia (NH3 ). However, N2 adsorption and *NN protonation for N2 activation reaction with the competing hydrogen evolution reaction remain a daunting challenge. Herein, a defect-rich TiO2 nanosheet electrocatalyst with PdCu alloy nanoparticles (PdCu/TiO2-x ) is designed to elucidate the reactivity and selectivity trends of N2 cleavage path for N2 -to-NH3 catalytic conversion. The introduction of oxygen vacancy (OV) not only acts as active sites but also effectively promotes the electron transfer from Pd-Cu sites to high-concentration Ti3+ sites, and thus lends to the N2 activation via electron donation of PdCu. OVs-mediated control effectively lowers the reaction barrier of *N2 H and *H adsorption and facilitates the first hydrogenation process of N2 activation. Consequently, PdCu/TiO2-x catalyst attains a high rate of NH3 evolution, reaching 5.0 mmol gcat. -1  h-1 . This work paves a pathway of defect-engineering metal-supported electrocatalysts for high-efficient ammonia electrosynthesis.

Accelerating multielectron reduction at CuxO nanograins interfaces with controlled local electric field.

Regulating electron transport rate and ion concentrations in the local microenvironment of active site can overcome the slow kinetics and unfavorable thermodynamics of CO2 electroreduction. However, simultaneous optimization of both kinetics and thermodynamics is hindered by synthetic constraints and poor mechanistic understanding. Here we leverage laser-assisted manufacturing for synthesizing CuxO bipyramids with controlled tip angles and abundant nanograins, and elucidate the mechanism of the relationship between electron transport/ion concentrations and electrocatalytic performance. Potassium/OH- adsorption tests and finite element simulations corroborate the contributions from strong electric field at the sharp tip. In situ Fourier transform infrared spectrometry and differential electrochemical mass spectrometry unveil the dynamic evolution of critical *CO/*OCCOH intermediates and product profiles, complemented with theoretical calculations that elucidate the thermodynamic contributions from improved coupling at the Cu+/Cu2+ interfaces. Through modulating the electron transport and ion concentrations, we achieve high Faradaic efficiency of 81% at ~900 mA cm-2 for C2+ products via CO2RR. Similar enhancement is also observed for nitrate reduction reaction (NITRR), achieving 81.83 mg h-1 ammonia yield rate per milligram catalyst. Coupling the CO2RR and NITRR systems demonstrates the potential for valorizing flue gases and nitrate wastes, which suggests a practical approach for carbon-nitrogen cycling.

Plaque enhancement predicts recurrence in acute ischemic stroke patients with large artery intracranial atherosclerosis.

BACKGROUND: The association between the degree of plaque enhancement and ischemic brain stroke recurrence remains unclear. We aimed to establish models to predict plaque enhancement and stroke recurrence. METHODS: Seventy-eight participants with acute ischemic brain stroke due to intracranial arterial stenosis were recruited and divided into high enhancement (HE) and non-HE groups. The relationship between imaging characteristics (degree of stenosis, minimal lumen area, intraplaque hemorrhage, and plaque burden) and the degree of plaque contrast enhancement was analyzed. Inflammatory cytokine expression was examined by flow cytometry. Independent predictors of stroke recurrence were investigated via multivariate Cox proportional hazards regression analysis. Nomogram was used to construct a prediction model. Harrell's concordance indices (c-indices) and calibration curves were used to assess the discrimination of the nomogram. A risk prediction nomogram for prognosis was constructed. RESULTS: Thirty-three participants were assigned to the HE group and 45 to the non-HE group. The degree of stenosis and plaque burden in the HE group was higher than that in the non-HE group (P<0.05). Multiple linear regression analysis showed the degree of stenosis was associated with HE (ß=0.513; P=0.000). After adjusting for confounding factors, age (HR=1.115; 95%CI=1.034-1.203, P=0.005) and HE plaques (HR=10.457; 95%CI=1.176-93.018; P=0.035) were independent risk factors of stroke recurrence, whereas cytokine levels were not statistically significant between two group. CONCLUSIONS: HE of intracranial atherosclerosis plaques is an independent factor for ischemic brain stroke recurrence.

Two-Dimensional Peripheral Refraction and Higher-Order Wavefront Aberrations Induced by Orthokeratology Lenses Decentration.

Purpose: The purpose of this study was to explore two-dimensional peripheral refraction and higher-order aberrations (HOAs) induced by orthokeratology lens decentration. Methods: Two-dimensional peripheral refraction and HOAs in a rectangular field (horizontally 60 degrees and vertically 36 degrees) were obtained using an open-view Hartmann-Shack wavefront sensor. The peripheral field was divided into 8 regions according to a combination of superior (UZ) or inferior (LZ) and a value, 1 (T25 to T30), 2 (T20 to T25), 3 (N20 to N25), or 4 (N25 to N30). The decentration of the lens was evaluated based on the change of power in the front of the tangential corneal map. All measurements were taken at the baseline and 1 month after lens fitting. Results: In total, 134 myopic children (age = 12.47 ± 1.70 years, SER = -2.44 ± 1.10 diopters [D]) were recruited. In general, horizontally asymmetrical change was observed in relative peripheral refraction (RPR), spherical aberration (SA), and horizontal coma. The root-mean square of higher order aberration (RMSHOA) and vertical coma demonstrated radial symmetrical change and vertically asymmetric change, respectively. Relative peripheral myopia was significantly increased after the treatment, with more myopic refraction in the temporal side. RPR changes in UZ2, UZ3, UZ4, LZ1, and LZ2 were related to the amount of lens decentration (r ≈ 0.4, P < 0.05). All HOAs increased after lens fitting (around 0.03 um, 0.02 um, 0.04 um, and 0.41 um for SA, horizontal COMA, vertical COMA, and RMSHOA in the periphery region). Conclusions: RPR and HOAs are related to lens decentration, which might contribute to the efficacy of orthokeratology. Translational Relevance: The study found a decentration-related optical feature after 1 month of lens wear, which is a suggested protective factor in myopia treatment. The findings might provide new insights for customized contact lens myopia treatment based on optics.

Characteristics of the Ocular Surface in Myopic Child Candidates of Orthokeratology Lens Wear.

INTRODUCTION: The purpose of this study was to investigate the characteristics of objective ocular surface parameters using non-invasive objective instruments in children with myopia who are candidates for orthokeratology lens wear. METHODS: Children with myopia who are candidates for orthokeratology lens wear were retrospectively investigated. The subjects were divided into three age groups. The Keratograph 5M and LipiView interferometry were used to assess non-invasive tear meniscus height (TMH), non-invasive tear film break-up time (NIBUT), conjunctival hyperemia redness score (RS), meibomian gland loss (MGL) score, lipid layer thickness (LLT), and blink pattern analysis, including the number of partial blinks (PB) and total blinks (TB), as well as the partial blink rate (PBR). RESULTS: A total of 1119 children with myopia (2070 eyes) aged 7-18 years were selected. The mean TMH, NIBUT, and LLT of the subjects was 0.21 mm, 12.45 s, and 65.28 nm, respectively. The mean RS and upper and lower MGL scores were 0.64, 1.00, and 1.06, respectively. The mean PB, TB, and PBR was 5.13, 6.46, and 0.81, respectively. Age was significantly correlated to all ocular surface parameters (p = 0.00), except for PB. NIBUT and LLT did not differ between male participants and female participants (all p > 0.05). TMH, RS, and upper and lower MGL were significantly higher in male participants than in female participants (all p < 0.01). In addition, NIBUT was positively associated with TMH (r = 0.13, p = 0.00) and LLT (r = 0.28, p = 0.00). Both upper and lower MGL were positively correlated with TMH, PB, and TB (all p = 0.00), whereas upper MGL was negatively correlated with NIBUT and LLT (all p < 0.05). TB was negatively correlated with NIBUT and LLT (all p = 0.00). PB had no relation with TMH, NIBUT, and LLT (all p > 0.05). In addition, PBR was positively correlated with NIBUT and LLT (all p = 0.00) but not with TMH, RS, or MGL (all p > 0.05). Overall, 57.00% had a TMH ≤ 0.2 mm, 43.20% had a NIBUT ≤ 10 s, 48.10% had an LLT ≤ 60 nm, and 88.10% had a PBR > 0.4. CONCLUSIONS: Child orthokeratology candidates have enhanced tear secretion and increased meibomian gland deficiency with aging. In addition, the adult dry eye diagnostic criteria may apply to orthokeratology candidates aged 12-18 years but should be lower for younger candidates. Given the proportion of abnormal risk, it is necessary to assess tear film status and blink pattern by reliable and feasible objective examination before fitting orthokeratology.

Short-term application of diquafosol ophthalmic solution benefits children with dry eye wearing orthokeratology lens.

Purpose: This aim of this study was to evaluate the effect of 3% Diquafosol Ophthalmic Solution (DQS) on children with dry eye from wearing overnight orthokeratology (OrthoK) lenses. Methods: Myopic children aged 8-18 years with dry eye syndrome were enrolled in this prospective observational study, and they were grouped according to their OrthoK treatment history for at least 1 year. All participants received DQS 4 times per day for 1 month. The following indicators were measured at baseline 1 month after treatment: the Dry Eye Questionnaire-5 (DEQ-5), non-invasive tear meniscus height (TMH), non-invasive tear film break-up time (first and average, NIBUT-F and NIBUT-A), meibomian gland score (MG score), conjunctival hyperemia redness score (R-scan), and blink pattern analysis. Results: A total of 104 participants (189 eyes) including 40 OrthoK wearers (72 eyes) and 64 Orthok candidates (117 eyes) completed the study. Of all, after DQS treatment for 1 month, DEQ-5 scores reduced from 5.54 ± 3.25 to 3.85 ± 2.98 (t = -3.36, p = 0.00). TMH increased from 0.20 ± 0.05 mm to 0.21 ± 0.05 mm (t = 2.59, p = 0.01), NIBUT-F and NIBUT-A were prolonged from 6.67 ± 4.71 s to 10.32 ± 6.19 s and from 8.86 ± 5.25 s to 13.30 ± 6.03 s (all p = 0.00), respectively. R-scan decreased from 0.69 ± 0.28 to 0.50 ± 0.25 (t = -9.01, p = 0.00). Upper MG scores decreased from 1.04 ± 0.32 to 0.97 ± 0.36 (t = -2.14, p = 0.03). Lower MG scores, partial blink rate, partial blinks, and total blinks did not change significantly. Both break-up time (BUT) and R-scan improved significantly after DQS treatment for 1 month (all p = 0.00) in OrthoK candidates and OrthoK wearers. Among the OrthoK wearers, TMH and dry eye symptoms increased significantly (all p = 0.00) but did not increase in OrthoK candidates (p > 0.05). There were no adverse events related to DQS. Conclusion: Diquafosol Ophthalmic Solution was effective for children wearing overnight orthokeratology in relieving dry eye symptoms and improving ocular surface parameters, which may help improve children's OrthoK wearing tolerance and compliance.

Preparation of a Three-Dimensional Composite Structure Based on a Periodic Au@Ag Core-Shell Nanocube with Ultrasensitive Surface-Enhanced Raman Scattering for Rapid Detection.

The absorption and scattering frequencies of surface plasmon resonance can be selectively adjusted by changing the morphology, size, structure, arrangement, and gap between noble metal nanoparticles so that the local electromagnetic field on the substrate surface can be further enhanced. This change will promote and popularize surface-enhanced Raman spectroscopy. This paper reports the research results and improvement scheme of surface enhanced Raman scattering (SERS) activity of silver-coated gold nanocubed/organism (Au@Ag/CW NCs) prepared by three-phase self-assembly. In the experiment, the uppermost oil phase in the three-phase self-assembly process was optimized as ethanol and n-hexane solution containing a specific concentration of a probe molecule rhodamine 6G or aspartame. The probe molecules were directly self-assembled on the surface of the composite substrate to avoid the possible loss and pollution during immersion and preservation and achieve the purpose of rapid detection. The results show that the Au@Ag/CW NC array substrate is a periodic cubic ring structure. The sensitivity, uniformity, reproducibility, and stability of composite Au@Ag/CW NC array substrates are verified by comparing the Raman activities of various substrates. The feasibility of using the substrate to realize rapid SERS detection, compared with the advantages and disadvantages of the traditional soaking method, proved that the prepared substrate and improvement direction have excellent potential for application and development prospects in the field of rapid food additive detection.

Enhancing nitrate attenuation in groundwater via selectively applying surface agricultural practices: A novel and sustainable strategy for non-point source pollution mitigation.

Non-point nitrate pollution in groundwater has been accelerated by agricultural development, but sustainable nitrogen removal is a challenge because of its wide distribution and negative side effects. Surface agricultural practices (SAPs), which are demonstrably effective in driving the downward infiltration of dissolved organic carbon (DOC), have not been well explored for their potential to enhance nitrate attenuation in groundwater. Therefore, a combination of soil column and groundwater incubation experiments was performed to investigate the carbon and nitrogen responses to different SAPs (manure fertilization, lucerne planting, and straw return). The soil column experiment showed that SAPs promoted DOC and reduced nitrate leaching into groundwater, and straw treatment witnessed the highest DOC leaching flux (252.71 g m-2 yr-1) and lowest nitrate leaching flux (9.51 g m-2 yr-1). The groundwater incubation experiment showed that leachates from the straw treatment displayed the best denitrification-enhancement performance, with the highest NO3--N reduction efficiency (92.93%) and rate (1.627 mg/day), N2 selectivity (99.78%), and net nitrogen removal (0.09 mg). Furthermore, Fourier transform ion cyclotron resonance mass spectrometry confirmed that CHOS molecules with lower double bond equivalents (0-5) and larger carbon numbers (10-15) were more accessible to denitrifiers. This study provides a new path for the sustainable control of non-point source nitrate pollution.

Highly Stable Pt-Based Oxygen Reduction Electrocatalysts toward Practical Fuel Cells: Progress and Perspectives.

The high cost and poor reliability of cathodic electrocatalysts for the oxygen reduction reaction (ORR), which requires significant amounts of expensive and scarce platinum, obstructs the broad applications of proton exchange membrane fuel cells (PEMFCs). The principles of ORR and the reasons for the poor stability of Pt-based catalysts are reviewed. Moreover, this paper discusses and categorizes the strategies for enhancing the stability of Pt-based catalysts in fuel cells. More importantly, it highlights the recent progress of Pt-based stability toward ORR, including surface-doping, intermetallic structures, 1D/2D structures, rational design of support, etc. Finally, for atomic-level in-depth information on ORR catalysts in fuel cells, potential perspectives are suggested, such as large-scale preparation, advanced interpretation techniques, and advanced simulation. This review aims to provide valuable insights into the fundamental science and technical engineering for practical Pt-based ORR electrocatalysts in fuel cells.

Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma.

OBJECTIVE: Therapy-induced tumour microenvironment (TME) remodelling poses a major hurdle for cancer cure. As the majority of patients with hepatocellular carcinoma (HCC) exhibits primary or acquired resistance to antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) therapies, we aimed to investigate the mechanisms underlying tumour adaptation to immune-checkpoint targeting. DESIGN: Two immunotherapy-resistant HCC models were generated by serial orthotopic implantation of HCC cells through anti-PD-L1-treated syngeneic, immunocompetent mice and interrogated by single-cell RNA sequencing (scRNA-seq), genomic and immune profiling. Key signalling pathway was investigated by lentiviral-mediated knockdown and pharmacological inhibition, and further verified by scRNA-seq analysis of HCC tumour biopsies from a phase II trial of pembrolizumab (NCT03419481). RESULTS: Anti-PD-L1-resistant tumours grew >10-fold larger than parental tumours in immunocompetent but not immunocompromised mice without overt genetic changes, which were accompanied by intratumoral accumulation of myeloid-derived suppressor cells (MDSC), cytotoxic to exhausted CD8+ T cell conversion and exclusion. Mechanistically, tumour cell-intrinsic upregulation of peroxisome proliferator-activated receptor-gamma (PPARγ) transcriptionally activated vascular endothelial growth factor-A (VEGF-A) production to drive MDSC expansion and CD8+ T cell dysfunction. A selective PPARγ antagonist triggered an immune suppressive-to-stimulatory TME conversion and resensitised tumours to anti-PD-L1 therapy in orthotopic and spontaneous HCC models. Importantly, 40% (6/15) of patients with HCC resistant to pembrolizumab exhibited tumorous PPARγ induction. Moreover, higher baseline PPARγ expression was associated with poorer survival of anti-PD-(L)1-treated patients in multiple cancer types. CONCLUSION: We uncover an adaptive transcriptional programme by which tumour cells evade immune-checkpoint targeting via PPARγ/VEGF-A-mediated TME immunosuppression, thus providing a strategy for counteracting immunotherapeutic resistance in HCC.