BNIP3-mediated mitophagy boosts the competitive growth of Lenvatinib-resistant cells via energy metabolism reprogramming in HCC.

An increasing evidence supports that cell competition, a vital selection and quality control mechanism in multicellular organisms, is involved in tumorigenesis and development; however, the mechanistic contributions to the association between cell competition and tumor drug resistance remain ill-defined. In our study, based on a contructed lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obvious competitive growth dominance over sensitive cells through reprogramming energy metabolism. Mechanistically, the hyperactivation of BCL2 interacting protein3 (BNIP3) -mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis, by regulating AMP-activated protein kinase (AMPK) -enolase 2 (ENO2) signaling, which perpetually maintaining lenvatinib-resistant HCC cells' competitive advantage over sensitive HCC cells. Of note, BNIP3 inhibition significantly sensitized the anti-tumor efficacy of lenvatinib in HCC. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism reprogramming; meanwhile, this work recognizes BNIP3 as a promising target to overcome HCC drug resistance.

Photocatalytic Formamide Synthesis via Coupling of Electrophilic and Nucleophilic Radicals over Atomically Dispersed Bi Sites.

Formamide (HCONH2) plays a pivotal role in the manufacture of a diverse array of chemicals, fertilizers, and pharmaceuticals. Photocatalysis holds great promise for green fabrication of carbon-nitrogen (C-N) compounds owing to its environmental friendliness and mild redox capability. However, the selective formation of the C-N bond presents a significant challenge in the photocatalytic synthesis of C-N compounds. This work developed a photocatalytic radical coupling method for the formamide synthesis from co-oxidation of ammonia (NH3) and methanol (CH3OH). An exceptional formamide yield rate of 5.47 ± 0.03 mmol·gcat-1·h-1 (911.87 ± 0.05 mmol·gBi-1·h-1) was achieved over atomically dispersed Bi sites (BiSAs) on TiO2. An accumulation of 45.0 mmol·gcat-1 (0.2 g·gcat-1) of formamide was achieved after long-term illumination, representing the highest level of photocatalytic C-N compounds synthesis. The critical C-N coupling for formamide formation originated from the "σ-σ" interaction between electrophilic ●CH2OH with nucleophilic ●NH2 radical. The  BiSAs sites facilitated the electron transfer between reactants and photocatalysts and enhanced the nucleophilic attack of â—NH2 radical at the â—CH2OH radical, thereby advancing the selective C-N bond formation. This work deepens the understanding of the C-N coupling mechanism and offers an alternative and intriguing photocatalytic approach for the efficient and sustainable production of C-N compounds.

Efficacy and safety assessment of traditional Chinese patent medicine for dyslipidemia: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.

Background: The overall prevalence of dyslipidemia continues to increase, which poses a significant risk for coronary artery disease. Some patients with dyslipidemia do not respond to or benefit from conventional lipid-lowering therapy, which warrants the need for alternative and complementary therapies. Chinese patent medicine (CPM) has shown great potential in the treatment of dyslipidemia, but its clinical value needs to be further explored. This study aims to systematically evaluate the efficacy and safety of CPM in treating dyslipidemia. Methods: This study was registered in INPLASY as INPLASY202330090. The randomized controlled trials included in this study were published in January 2013 to March 2023 and retrieved from the Web of Science, PubMed, Embase, Cochrane Library, SinoMed, China National Knowledge Internet, WanFang, and VIP. The bias risk in the study was independently evaluated by two reviewers using the Cochrane Randomized Trial Bias Risk Tool (RoB 2) Review Manager 5.4 software was used for the overall effect analysis and subgroup analysis of four blood lipids, and the trial sequential analysis (TSA) was conducted to check the results. Results: A total of 69 studies were included, involving 6,993 participants. The methodological quality was in the middle level. Meta-analysis showed that CPM markedly improved the levels of total cholesterol (TC) [mean difference (MD) =-0.54 mmol/L; 95% confidence interval (CI): -0.71 to -0.37; P<0.001], triglyceride (TG) (MD =-0.43 mmol/L; 95% CI: -0.53 to -0.33; P<0.001), low-density lipoprotein cholesterol (LDL-C) (MD =-0.40 mmol/L; 95% CI: -0.50 to -0.30; P<0.001) and increased levels of high-density lipoprotein cholesterol (HDL-C) (MD =0.23 mmol/L; 95% CI: 0.18 to 0.27; P<0.001), in patients with dyslipidemia. Though CPM did not differ significantly from statins when used alone, it could improve lipid profile better in all cases when used in combination with statins and with drugs used for comorbidities or co-morbidities. Subgroup analysis found that the efficacy of pill formulations was superior to other formulations, and CPM showed better lipid-lowering response in the context of comorbidity. The TSA confirmed the robustness of the analysis of the LDL-C level. No significant difference was observed in the incidence of adverse events between the treatment group and the control group [risk ratio (RR) =0.89; 95% CI: 0.69-1.16; P=0.40]. Conclusions: CPM can yield superior therapeutic effects in ameliorating dyslipidemia without exacerbating adverse effects as an alternative and complementary therapy. In addition, the therapeutic effect can be improved by emphasizing pill formulation and strengthening the standardization of syndromes.

Frequency-dependent effects of 0.05% atropine eyedrops on myopia progression and peripheral defocus: a prospective study.

BACKGROUND: Atropine, specifically 0.05% eyedrops, has proven effective in slowing myopia progression. This study aims to investigate peripheral refraction (PR) characteristics in myopic children treated with 0.05% atropine eyedrops at different frequencies. METHODS: One hundred thirty-eight myopic children completed this one-year prospective study, randomly assigned to once daily (7/7), twice per week (2/7), or once per week (1/7) groups. Spherical equivalent (SE) and axial length (AL) were measured. PR was assessed using a custom-made Hartmann-Shack wavefront peripheral sensor, covering a visual field of horizontal 60° and vertical 36°. Relative peripheral refraction (RPR) was calculated by subtracting central from peripheral measurements. RESULTS: After one year, SE increased more significantly in the 1/7 group compared to the 7/7 group (P < 0.001) and 2/7 group (P = 0.004); AL elongation was also greater in the 1/7 group compared to the 7/7 group (P < 0.001). In comparison with higher frequency groups, 1/7 group exhibited more myopic PR in the fovea and its vertical superior, inferior, and nasal retina; and less myopic RPR in the periphery retina after one-year (P < 0.05). Additionally, RPR in the 7/7 group demonstrated myopic shift across the entire retina, the 2/7 group in temporal and inferior retina, while the 1/7 group showed a hyperopic shift in the superior retina (P < 0.05). Moreover, myopic shift of RPR in the temporal retina is related to less myopia progression, notably in the 7/7 group (P < 0.05). CONCLUSIONS: Atropine inhibits myopia progression in a frequency-dependent manner. The once-daily group showed the slowest myopia progression but exhibited more myopic shifts in RPR. Additionally, RPR in the temporal retina was related to myopia progression in all groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100043506. Registered 21 February 2021, https://www.chictr.org.cn/showproj.html?proj=122214.

PPP1R15A-expressing monocytic MDSCs promote immunosuppressive liver microenvironment in fibrosis-associated hepatocellular carcinoma.

Background & Aims: Recent studies demonstrated the importance of fibrosis in promoting an immunosuppressive liver microenvironment and thereby aggressive hepatocellular carcinoma (HCC) growth and resistance to immune checkpoint blockade (ICB), particularly via monocyte-to-monocytic myeloid-derived suppressor cell (M-MDSC) differentiation triggered by hepatic stellate cells (HSCs). We thus aimed to identify druggable targets in these immunosuppressive myeloid cells for HCC therapy. Methods: M-MDSC signature genes were identified by integrated transcriptomic analysis of a human HSC-monocyte culture system and tumor-surrounding fibrotic livers of patients with HCC. Mechanistic and functional studies were conducted using in vitro-generated and patient-derived M-MDSCs. The therapeutic efficacy of a M-MDSC targeting approach was determined in fibrosis-associated HCC mouse models. Results: We uncovered over-expression of protein phosphatase 1 regulatory subunit 15A (PPP1R15A), a myeloid cell-enriched endoplasmic reticulum stress modulator, in human M-MDSCs that correlated with poor prognosis and ICB non-responsiveness in patients with HCC. Blocking TGF-ß signaling reduced PPP1R15A expression in HSC-induced M-MDSCs, whereas treatment of monocytes by TGF-ß upregulated PPP1R15A, which in turn promoted ARG1 and S100A8/9 expression in M-MDSCs and reduced T-cell proliferation. Consistently, lentiviral-mediated knockdown of Ppp1r15a in vivo significantly reduced ARG1+S100A8/9+ M-MDSCs in fibrotic liver, leading to elevated intratumoral IFN-γ+GZMB+CD8+ T cells and enhanced anti-tumor efficacy of ICB. Notably, pharmacological inhibition of PPP1R15A by Sephin1 reduced the immunosuppressive potential but increased the maturation status of fibrotic HCC patient-derived M-MDSCs. Conclusions: PPP1R15A+ M-MDSC cells are involved in immunosuppression in HCC development and represent a novel potential target for therapies. Impact and implications: Our cross-species analysis has identified PPP1R15A as a therapeutic target governing the anti-T-cell activities of fibrosis-associated M-MDSCs (monocytic myeloid-derived suppressor cells). The results from the preclinical models show that specific inhibition of PPP1R15A can break the immunosuppressive barrier to restrict hepatocellular carcinoma growth and enhance the efficacy of immune checkpoint blockade. PPP1R15A may also function as a prognostic and/or predictive biomarker in patients with hepatocellular carcinoma.

Phosphorus-Doping Enables the Superior Durability of a Palladium Electrocatalyst towards Alkaline Oxygen Reduction Reactions.

The sluggish kinetics of oxygen reduction reactions (ORRs) require considerable Pd in the cathode, hindering the widespread of alkaline fuel cells (AFCs). By alloying Pd with transition metals, the oxygen reduction reaction's catalytic properties can be substantially enhanced. Nevertheless, the utilization of Pd-transition metal alloys in fuel cells is significantly constrained by their inadequate long-term durability due to the propensity of transition metals to leach. In this study, a nonmetallic doping strategy was devised and implemented to produce a Pd catalyst doped with P that exhibited exceptional durability towards ORRs. Pd3P0.95 with an average size of 6.41 nm was synthesized by the heat-treatment phosphorization of Pd nanoparticles followed by acid etching. After P-doping, the size of the Pd nanoparticles increased from 5.37 nm to 6.41 nm, and the initial mass activity (MA) of Pd3P0.95/NC reached 0.175 A mgPd-1 at 0.9 V, slightly lower than that of Pd/C. However, after 40,000 cycles of accelerated durability testing, instead of decreasing, the MA of Pd3P0.95/NC increased by 6.3% while the MA loss of Pd/C was 38.3%. The durability was primarily ascribed to the electronic structure effect and the aggregation resistance of the Pd nanoparticles. This research also establishes a foundation for the development of Pd-based ORR catalysts and offers a direction for the future advancement of catalysts designed for practical applications in AFCs.

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%.

1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets.

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.