Benzaldehyde stimulates autophagy via the sonic hedgehog signaling pathway in mouse brain astrocytes after treatment with Angiostrongylus cantonensis excretory-secretory products.

Autophagy is a vital cellular process responsible for digesting various cytoplasmic organelles. This process plays a crucial role in maintaining cell survival and homeostasis, especially under conditions that cause nutrient deficiency, cellular damage, and oxidative stress. Neuroangiostrongyliasis is an infection caused by the parasitic nematode Angiostrongylus cantonensis and is considered as an emerging disease in many parts of the world. However, effective therapeutic strategies for neuroangiostrongyliasis still need to be further developed. In this study, we investigated the effects of benzaldehyde treatment on autophagy and sonic hedgehog (Shh) signaling in A. cantonensis-infected mice and its mechanisms. First, we found autophagosome generation in the central nervous system after A. cantonensis infection. Next, benzaldehyde combined with albendazole treatment reduced eosinophilic meningitis and upregulated the expression of Shh signaling- and autophagy-related molecules in A. cantonensis-infected mouse brains. In vitro experiments demonstrated that benzaldehyde could induce autophagy via the Shh signaling pathway in A. cantonensis excretory-secretory products (ESPs)-treated mouse astrocytes. Finally, benzaldehyde treatment also decreased lipid droplet accumulation and increased cholesterol production by activating the Shh pathway after ESPs treatment. In conclusion, these findings suggested that benzaldehyde treatment could alleviate brain damage by stimulating autophagy generation through the Shh signaling pathway.

Robust discriminator of chiral molecules via a topological invariant.

We propose a scheme for chirality discrimination via a topological invariant. The physical model is based on a three-level subspace of a molecule. By modulating the components of the control field with proper frequencies, two different two-level effective Hamiltonians are derived for the left-handed and the right-handed molecules. We parameterize the effective Hamiltonians with two angles and demonstrate that a topological quantum phase transition can be induced by tuning the effective Rabi frequency if the molecule is right-handed. This phenomenon provides a method to discriminate the chirality of the molecule by measuring a topological invariant, i.e., the Chern number, of the parametric manifold. Since the Chern number is robust against perturbations to the system, the scheme is insensitive to the systematic errors of the control fields, the deviations of the modulation frequencies, and decoherence of the molecule. Therefore, the scheme may provide useful perspectives to construct a robust discriminator of chiral molecules.

Bridging the gap in cardiac mass diagnosis: Advanced imaging, genetic associations, and biomarkers.

In this editorial we comment on the article by Huffaker et al published in a recent issue of the World Journal of Clinical Cases. We focus on cardiac tumors linked to genetic syndromes and the differential diagnosis of cardiac masses. As cardiomyocytes lack the ability to actively divide, primary cardiac tumors are extremely rare across all ethnicities and age groups. Once they occur, these tumors are often associated with genetic mutations and, occasionally, genetic syndromes. This underscores the importance of considering genetic mutations and syndromes when encountering these cases. The more common growths in the heart are thrombi and vegetations, which can mimic tumors, further making the differential diagnosis challenging. Among the imaging techniques, contrast-enhanced cardiac magnetic resonance imaging has the highest sensitivity for differential diagnosis. To aid in the differential diagnosis of cardiac masses, especially thrombi, appropriate utilization of biomarkers (i.e. D-dimer level) may provide pivotal clinical implications. Employing a multidisciplinary approach that integrates personal history, epidemiological insights, imaging findings, genetic markers, and biomarkers is therefore critical in the diagnostic process of cardiac masses.

Local Injection of Stem Cells Can Be a Potential Strategy to Improve Bladder Dysfunction after Outlet Obstruction in Rats.

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-ß1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFß-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.

A simple model to predict early recurrence of hepatocellular carcinoma after liver resection.

PURPOSE: Multiple studies have reported models for predicting early recurrence of hepatocellular carcinoma (HCC) after liver resection (LR). However, these models are too complex to use in daily practice. We aimed to develop a simple model. METHOD: We enrolled 1133 patients with newly diagnosed HCC undergoing LR. The Kaplan - Meier method and log-rank test were used for survival analysis and Cox proportional hazards analysis to identify prognostic factors associated with early recurrence (i.e., recurrence within two years after LR). RESULTS: Early recurrence was identified in 403 (35.1%) patients. In multivariate analysis, alpha-fetoprotein (AFP) 20-399 vs. < 20 ng/ml (HR = 1.282 [95% confidence interval = 1.002-1.639]; p = 0.048); AFP ≥ 400 vs. < 20 ng/ml (HR = 1.755 [1.382-2.229]; p < 0.001); 7th edition American Joint Committee on Cancer (AJCC) stage 2 vs. 1 (HR = 1.958 [1.505-2.547]; p < 0.001); AJCC stage 3 vs. 1 (HR = 4.099 [3.043-5.520]; p < 0.001); and pathology-defined cirrhosis (HR = 1.46 [1.200-1.775]; p < 0.001) were associated with early recurrence. We constructed a predictive model with these variables, which provided three risk strata for recurrence-free survival (RFS): low risk, intermediate risk, and high risk, with two-year RFS of 79%, 57%, and 35%, respectively (p < 0.001). CONCLUSION: We developed a simple model to predict early recurrence risk for patients undergoing LR for HCC.

Production of γ-aminobutyric acid by immobilization of two Yarrowia lipolytica glutamate decarboxylases on electrospun nanofibrous membrane.

This study harnesses glutamate decarboxylase (GAD) from Yarrowia lipolytica to improve the biosynthesis of γ-aminobutyric acid (GABA), focusing on boosting the enzyme's catalytic efficiency and stability by immobilizing it on nanofibrous membranes. Through recombinant DNA techniques, two GAD genes, YlGAD1 and YlGAD2, were cloned from Yarrowia lipolytica and then expressed in Escherichia coli. Compared to their soluble forms, the immobilized enzymes exhibited significant improvements in thermal and pH stability and increased resistance to chemical denaturants. The immobilization notably enhanced substrate affinity, as evidenced by reduced Km values and increased kcat values, indicating heightened catalytic efficiency. Additionally, the immobilized YlGAD1 and YlGAD2 enzymes showed substantial reusability, maintaining 50% and 40% of their activity, respectively, after six consecutive cycles. These results underscore the feasibility of employing immobilized YlGAD enzymes for cost-effective and environmentally sustainable GABA production. This investigation not only affirms the utility of YlGADs in GABA synthesis but also underscores the advantages of enzyme immobilization in industrial settings, paving the way for scalable biotechnological processes.

Ti-Substituted O3-NaNi0.5Mn0.3Ti0.2O2 Material with a Disordered Transition Metal Layer and a Stable Structure.

O3-type NaNi0.5Mn0.5O2 (NNM) is very competitive for sodium-ion batteries (SIBs) due to its high capacity and easy production. Nevertheless, the intricate phase transitions during the charging-discharging significantly impede its practical application. This paper proposes a strategy for successfully synthesizing NaNi0.5Mn0.3Ti0.2O2 (NNMT) by combining coprecipitation and a high-temperature solid-state method. This method introduces Ti elements while retaining the electrochemically active Ni2+ content, thus, the NNMT has a high initial specific capacity of 151.4 mAh g-1 at 1 C. It is demonstrated that introducing Ti4+ leads to the transition metal layers becoming disordered by ex situ XRD, thus mitigating the irreversible phase transition of the material. In addition, Ti4+ does not have an outer electron, which can reduce electron delocalization in the transition metal layer and improve the material's cyclic stability. The NNMT possesses a capacity retention rate of 60.66% after 150 cycles, much higher than the initial NNM's 18.96%. It also exhibits an excellent discharge capacity of 86.8 mAh g-1 at 5 C. In conclusion, the cycling and rate performance of the Ti-substituted NNMT are greatly improved without capacity loss, which offers innovative concepts for the modification means of the SIBs layered oxide cathode materials.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

Purpose: The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Methods: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Results: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. Conclusions: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

Tracing residual patterns and microbial communities of pharmaceuticals and personal care products from 17 urban landfills leachate in China.

Landfill leachate contributes significantly to the presence of pharmaceuticals and personal care products (PPCPs) in the environment, and is a crucial source of contamination. To examine the occurrence of PPCPs and microbial communities, this study comprehensively investigated the concentrations of PPCPs and the abundance of microorganisms in the leachate from 17 municipal landfills across China. Generally, Lidocaine, Linear alkylbenzene sulfonate-C11, and Triclocarban, which are closely associated with human activities, exhibited a detection frequency of 100 % in the leachate. Driven by consumer demand, analgesic and antipyretic drugs have emerged as the most prominent PPCPs in leachate (accounting for 39.9 %). Notably, the Ibuprofen peaked at 56.3 µg/L. Regarding spatial distribution, the contamination of PPCPs in leachates from the eastern regions of China was significantly higher than that in other regions, owing to the level of economic development and demographic factors. Furthermore, the 16S rRNA results revealed significant differences in microbial communities among the leachates from different areas. Although the impact of PPCPs on microbial communities may not be as significant as that of environmental factors, most positive correlations between PPCPs and microorganisms indicate their potential role in providing nutrients and creating favorable conditions for microbial growth. Overall, this research offers new perspectives on the residual features of PPCPs and the microbial community structure in leachates from various regions in China.

Myeloid­derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in colorectal cancer (Review).

Globally, colorectal cancer (CRC) is the third most common type of cancer. CRC has no apparent symptoms in the early stages of disease, and most patients receive a confirmed diagnosis in the middle or late disease stages. The incidence of CRC continues to increase, and the affected population tends to be younger. Therefore, determining how to achieve an early CRC diagnosis and treatment has become a top priority for prolonging patient survival. Myeloid­derived suppressor cells (MDSCs) are a group of bone marrow­derived immuno­negative regulatory cells that are divided into two subpopulations, polymorphonuclear­MDSCs and monocytic­MDSCs, based on their phenotypic similarities to neutrophils and monocytes, respectively. These cells can inhibit the immune response and promote cancer cell metastasis in the tumour microenvironment (TME). A large aggregation of MDSCs in the TME is often a marker of cancer and a poor prognosis in inflammatory diseases of the intestine (such as colonic adenoma and ulcerative colitis). In the present review, the phenotypic classification of MDSCs in the CRC microenvironment are first discussed. Then, the amplification, role and metastatic mechanism of MDSCs in the CRC TME are described, focusing on genes, gene modifications, proteins and the intestinal microenvironment. Finally, the progress in CRC­targeted therapies that aim to modulate the quantity, function and structure of MDSCs are summarized in the hope of identifying potential screening markers for CRC and improving CRC prognosis and therapeutic options.

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

Human TMEFF1 is a restriction factor for herpes simplex virus in the brain.

Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.

CD5 deletion enhances the antitumor activity of adoptive T cell therapies.

Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.

Deep Learning Evaluation of Glaucoma Detection Using Fundus Photographs in Highly Myopic Populations.

OBJECTIVES: This study aimed to use deep learning to identify glaucoma and normal eyes in groups with high myopia using fundus photographs. METHODS: Patients who visited Tri-Services General Hospital from 1 November 2018 to 31 October 2022 were retrospectively reviewed. Patients with high myopia (spherical equivalent refraction of ≤-6.0 D) were included in the current analysis. Meanwhile, patients with pathological myopia were excluded. The participants were then divided into the high myopia group and high myopia glaucoma group. We used two classification models with the convolutional block attention module (CBAM), an attention mechanism module that enhances the performance of convolutional neural networks (CNNs), to investigate glaucoma cases. The learning data of this experiment were evaluated through fivefold cross-validation. The images were categorized into training, validation, and test sets in a ratio of 6:2:2. Grad-CAM visual visualization improved the interpretability of the CNN results. The performance indicators for evaluating the model include the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 3088 fundus photographs were used for the deep-learning model, including 1540 and 1548 fundus photographs for the high myopia glaucoma and high myopia groups, respectively. The average refractive power of the high myopia glaucoma group and the high myopia group were -8.83 ± 2.9 D and -8.73 ± 2.6 D, respectively (p = 0.30). Based on a fivefold cross-validation assessment, the ConvNeXt_Base+CBAM architecture had the best performance, with an AUC of 0.894, accuracy of 82.16%, sensitivity of 81.04%, specificity of 83.27%, and F1 score of 81.92%. CONCLUSIONS: Glaucoma in individuals with high myopia was identified from their fundus photographs.

The positive role of transforming growth factor-ß1 in ischemic stroke.

Ischemic stroke is one of the most disabling and fatal diseases around the world. The damaged brain tissues will undergo excessive autophagy, vascular endothelial cells injury, blood-brain barrier (BBB) impairment and neuroinflammation after ischemic stroke. However, there is no unified viewpoint on the underlying mechanism of brain damage. Transforming growth factor-ß1 (TGF-ß1), as a multi-functional cytokine, plays a crucial role in the intricate pathological processes and helps maintain the physiological homeostasis of brain tissues through various signaling pathways after ischemic stroke. In this review, we summarize the protective role of TGF-ß1 in autophagic flux, BBB, vascular remodeling, neuroinflammation and other aspects after ischemic stroke. Based on the review, we believe that TGF-ß1 could serve as a key target for treating ischemic stroke.

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Exposure to 1-nitropyrene after weaning induces anxiety-like behavior partially by inhibiting steroid hormone synthesis in prefrontal cortex.

1-Nitropyrene (1-NP) is a neurodevelopmental toxicant. This study was to evaluate the impact of exposure to 1-NP after weaning on anxiety-like behavior. Five-week-old mice were administered with 1-NP (0.1 or 1 mg/kg) daily for 4 weeks. Anxiety-like behaviour was measured using elevated-plus maze (EPM) and open field test (OFT). In EPM test, time spending in open arm and times entering open arm were reduced in 1-NP-treated mice. In OFT test, time spent in the center region and times entering the center region were diminished in 1-NP-treated mice. Prefrontal dendritic length and number of dendrite branches were decreased in 1-NP-treated mice. Prefrontal PSD95, an excitatory postsynaptic membrane protein, and gephyrin, an inhibitory postsynaptic membrane protein, were downregulated in 1-NP-treated mice. Further analysis showed that peripheral steroid hormones, including serum testosterone (T) and estradiol (E2), testicular T, and ovarian E2, were decreased in 1-NP-treated mice. Interestingly, T and E2 were diminished in 1-NP-treated prefrontal cortex. Prefrontal T and E2 synthases were diminished in 1-NP-treated mice. Mechanistically, GCN2-eIF2α, a critical pathway that regulates ribosomal protein translation, was activated in 1-NP-treated prefrontal cortex. These results indicate that exposure to 1-NP after weaning induces anxiety-like behaviour partially by inhibiting steroid hormone synthesis in prefrontal cortex.

The Application of Rho Kinase Inhibitors in the Management of Glaucoma.

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.

Design, synthesis, and anti-oomycete activity of 3-acyloxymaltol/ethyl maltol derivatives.

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.