Autophagy-targeting modulation to promote peripheral nerve regeneration.

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms. Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration. However, recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration, particularly in the context of traumatic injuries. Consequently, autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration. Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths, thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation. These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration. A range of autophagy-inducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries. This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration, summarizing the potential drugs and interventions that can be harnessed to promote this process. We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

Reflectance spectroscopy analysis and lithium content estimation in lithium-rich rocks and stream sediments: Insights from Tuanjie Peak, Western Kunlun, China.

Lithium, a rare metal of strategic importance, has garnered heightened global attention. This investigation delves into the laboratory visible-near infrared and short-wavelength infrared reflectance (VNIR-SWIR 350 nm-2500 nm) spectral properties of lithium-rich rocks and stream sediments, aiming to elucidate their quantitative relationship with lithium concentration. This research seeks to pave new avenues and furnish innovative technical solutions for probing sedimentary lithium reserves. Conducted in the Tuanjie Peak region of Western Kunlun, Xinjiang, China, this study analyzed 614 stream sediments and 222 rock specimens. Initial steps included laboratory VNIR-SWIR spectral reflectance measurements and lithium quantification. Following the preprocessing of spectral data via Savitzky-Golay (SG) smoothing and continuum removal (CR), the absorption positions (Pos2210nm, Pos1910nm) and depths (Depth2210, Depth1910) in the rock spectra, as well as the Illite Spectral Maturity (ISM) of the rock samples, were extracted. Employing both the Successive Projections Algorithm (SPA) and genetic algorithm (GA), wavelengths indicative of lithium content were identified. Integrating the lithium-sensitive wavelengths identified by these feature selection methods, A quantitative predictive regression model for lithium content in rock and stream sediments was developed using partial least squares regression (PLSR), support vector regression (SVR), and convolutional neural network (CNN). Spectral analysis indicated that lithium is predominantly found in montmorillonite and illite, with its content positively correlating with the spectral maturity of illite and closely related to Al-OH absorption depth (Depth2210) and clay content. The SPA algorithm was more effective than GA in extracting lithium-sensitive bands. The optimal regression model for quantitative prediction of lithium content in rock samples was SG-SPA-CNN, with a correlation coefficient prediction (Rp) of 0.924 and root-mean-square error prediction (RMSEP) of 0.112. The optimal model for the prediction of lithium content in stream sediment was SG-SPA-CNN, with an Rp and RMSEP of 0.881 and 0.296, respectively. The higher prediction accuracy for lithium content in rocks compared to sediments indicates that rocks are a more suitable medium for predicting lithium content. Compared to the PLSR and SVR models, the CNN model performs better in both sample types. Despite the limitations, this study highlights the effectiveness of hyperspectral technology in exploring the potential of clay-type lithium resources in the Tuanjie Peak area, offering new perspectives and approaches for further exploration.

High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. METHODS: A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. RESULTS: Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. CONCLUSIONS: Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.

Advances in Novel Biomaterial-Based Strategies for Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is a highly disabling neurological disorder. Its pathological process comprises an initial acute injury phase (primary injury) and a secondary injury phase (subsequent chronic injury). Although surgical, drug, and cell therapies have made some progress in treating SCI, there is no exact therapeutic strategy for treating SCI and promoting nerve regeneration due to the complexity of the pathological SCI process. The development of novel drug delivery systems to treat SCI is expected to significantly impact the individualized treatment of SCI due to its unique and excellent properties, such as active targeting and controlled release. In this review, we first describe the pathological progression of the SCI response, including primary and secondary injuries. Next, we provide a concise overview of newly developed nanoplatforms and their potential application in regulating and treating different pathological processes of SCI. Then, we introduce the existing potential problems and future clinical application perspectives of biomedical engineering-based therapies for SCI.

Investigating the shared genetic architecture between depression and subcortical volumes.

Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression and subcortical volumes remain inadequately understood. Here, we investigate the extent of polygenic overlap using the bivariate causal mixture model (MiXeR), leveraging summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 14 subcortical volumetric phenotypes (N = 33,224). Additionally, we identify shared genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that subcortical volumetric traits share a substantial proportion of genetic variants with depression, with 44 distinct shared loci identified by subsequent conjunctional FDR analysis. These shared loci are predominantly located in intronic regions (58.7%) and non-coding RNA intronic regions (25.4%). The 269 protein-coding genes mapped by these shared loci exhibit specific developmental trajectories, with the expression level of 55 genes linked to both depression and subcortical volumes, and 30 genes linked to cognitive abilities and behavioral symptoms. These findings highlight a shared genetic architecture between depression and subcortical volumetric phenotypes, enriching our understanding of the neurobiological underpinnings of depression.

Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells.

Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-ß-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.

Decline in carbon emission intensity of global agriculture has stagnated recently.

Using global data for around 180 countries and territories and 170 food/feed types primarily derived from FAOSTAT, we have systematically analyzed the changes in greenhouse gas (GHG) emission intensity (GHGi) (kg CO2eq per kg protein production) over the past six decades. We found that, with large spatial heterogeneity, emission intensity decreased by nearly two-thirds from 1961 to 2019, predominantly in the earlier years due to agronomic improvement in productivity. However, in the most recent decade, emission intensity has become stagnant, and in a few countries even showed an increase, due to the rapid increase in livestock production and land use changes. The trade of final produced protein between countries has potentially reduced the global GHGi, especially for countries that are net importers with high GHGi, such as many in Africa and South Asia. Overall, a continuous decline of emission intensity in the future relies on countries with higher emission intensity to increase agricultural productivity and minimize land use changes. Countries with lower emission intensity should reduce livestock production and increase the free trade of agricultural products and improve the trade optimality.

Head and neck cancer: pathogenesis and targeted therapy.

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early-stage HNC. For recurrent or metastatic (R/M) HNC, the first-line treatment is platinum-based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody-drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.

Anti-HIV activity in traditional Chinese medicine: clinical implications of monomeric herbal remedies and compound decoctions.

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

Unraveling multi-scale neuroimaging biomarkers and molecular foundations for schizophrenia: A combined multivariate pattern analysis and transcriptome-neuroimaging association study.

AIMS: Schizophrenia is characterized by alterations in resting-state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia. METHODS: A cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting-state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel-level (Scale 1) and regional-level (Scales 2-4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome-neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia. RESULTS: The ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome-neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity. CONCLUSIONS: This study highlights the potential of multi-scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia.

Solvothermal synthesis of PdCu nanorings with high catalytic performance for alcohol electrooxidation.

Two-dimensional (2D) Pd-based nanostructures with a high active surface area and a large number of active sites are commonly used in alcohol oxidation research, whereas the less explored ring structure made of nanosheets with large pores is of interest. In this study, we detail the fabrication of PdCu nanorings (NRs) featuring hollow interiors and low coordinated sites using a straightforward solvothermal approach. Due to increased exposure of active sites and the synergistic effects of bimetallics, the PdCu NRs exhibited superior catalytic performance in both the ethanol oxidation reaction (EOR) and the ethylene glycol oxidation reaction (EGOR). The mass activities of PdCu NRs for EOR and EGOR were measured at 7.05 A/mg and 8.12 A/mg, respectively, surpassing those of commercial Pd/C. Furthermore, the PdCu NRs demonstrated enhanced catalytic stability, maintaining higher mass activity levels compared to other catalysts during stability testing. This research offers valuable insights for the development of efficient catalysts for alcohol oxidation.

The Mitogenomic Landscape of Hexacorallia Corals: Insight into Their Slow Evolution.

The utility of the mitochondrial genomes (mitogenomes) in analyzing the evolutionary history of animals has been proven. Five deep-sea corals (Bathypathes sp.1, Bathypathes sp.2, Schizopathidae 1, Trissopathes sp., and Leiopathes sp.) were collected in the South China Sea (SCS). Initially, the structures and collinearity of the five deep-sea coral mitogenomes were analyzed. The gene arrangements in the five deep-sea coral mitogenomes were similar to those in the order Antipatharia, which evidenced their conservation throughout evolutionary history. Additionally, to elucidate the slow evolutionary rates in Hexacorallia mitogenomes, we conducted comprehensive analyses, including examining phylogenetic relationships, performing average nucleotide identity (ANI) analysis, and assessing GC-skew dissimilarity combining five deep-sea coral mitogenomes and 522 reference Hexacorallia mitogenomes. Phylogenetic analysis using 13 conserved proteins revealed that species clustered together at the order level, and they exhibited interspersed distributions at the family level. The ANI results revealed that species had significant similarities (identity > 85%) within the same order, while species from different orders showed notable differences (identity < 80%). The investigation of the Hexacorallia mitogenomes also highlighted that the GC-skew dissimilarity was highly significant at the order level, but not as pronounced at the family level. These results might be attributed to the slow evolution rate of Hexacorallia mitogenomes and provide evidence of mitogenomic diversity. Furthermore, divergence time analysis revealed older divergence times assessed via mitogenomes compared with nuclear data, shedding light on significant evolutionary events shaping distinct orders within Hexacorallia corals. Those findings provide new insights into understanding the slow evolutionary rates of deep-sea corals in all lineages of Hexacorallia using their mitogenomes.

[Corrigendum] Knockdown of circ_0067934 inhibits gastric cancer cell proliferation, migration and invasion via the miR­1301­3p/KIF23 axis.

Following the publication of the above article, an interested reader drew to our attention the fact that the forward primer reported in Table I on p. 3 for miR­545­3p (5'­TGGCTCAGTTCAGCAGGAAC­3') was actually for miR­24­3p (5'­UGGCUCAGUUCAGCAGGAACAG­3'). Upon performing an independent analysis of the primer sequences in the Editorial Office, the sequence presented for miR­670­5p also appeared to have potentially been written incorrectly. After having drawn these matters to the attention of the authors, they realized that these sequences had indeed been written incorrectly in Table I.  The corrected version of Table I, featuring the correct forward and reverse primer sequences for both miR­670­5p and miR­545­3p, is shown opposite. The authors wish to thank the interested reader for drawing this error to their attention, and are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 202, 2022; DOI: 10.3892/mmr.2022.12718].

Healthy Sleep Pattern, Metabolic Diseases, and Risk of Stroke: The Kailuan Cohort Study.

Background: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited. Objective: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association. Methods: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7-8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association. Results: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke. Conclusion: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.

Hypoxia Stimulates PYGB Enzymatic Activity to Promote Glycogen Metabolism and Cholangiocarcinoma Progression.

Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.

The effect of active and passive smoking during pregnancy on birth outcomes: A cohort study in Shanghai.

INTRODUCTION: China is the largest tobacco consumer in the world, and tobacco poses a serious threat to the health of pregnant women. However, there are relatively few domestic studies on smoking during pregnancy and childbirth outcomes among pregnant women. The purpose of this study was to analyze the effect of active and passive smoking on pregnant women and their pregnancy outcomes, providing evidence and recommendations for intervention measures. METHODS: This was a cohort study in Shanghai from April 2021 to September 2023. According to the smoking status of pregnant women, they were divided into three groups: active smokers, passive smokers and non-smokers. A self-designed questionnaire was utilized to conduct the survey, and their pregnancy outcomes were tracked and followed up. RESULTS: A total of 3446 pregnant women were included in this study, among which 2.1% were active smokers, 43.5% were passive smokers, and 54.4% were non-smokers. The average age of the pregnant women was 29.9 years, and 41.2% had a university degree or higher. The education level of active smokers and passive smokers was significantly lower than that of non-smokers (p<0.05).The average gestational age of non-smokers was 38.6 weeks, and the birth weight was 3283.2 g, which was higher than those of active smokers and passive smokers (p<0.05). Logistic regression analysis showed that passive smoking increased the likelihood of preterm birth (AOR=1.38; 95% CI: 1.05-1.81), low birth weight (AOR=1.53; 95% CI: 1.10-2.12), and intrauterine growth restriction (AOR=1.35; 95% CI: 1.02-1.79), while active smoking increased the likelihood of preterm birth (AOR=2.98; 95% CI: 1.50-5.90), low birth weight (AOR=4.29; 95% CI: 2.07-8.88), intrauterine growth restriction (AOR=2.70; 95% CI: 1.37-5.33) , and birth defects (AOR=2.66; 95% CI: 1.00-6.97). CONCLUSIONS: Our findings illustrate that active and passive smoking can lead to adverse pregnancy outcomes. This study provides data on the relationship between smoking during pregnancy and delivery outcomes among pregnant women. In the future, we need more effective strategies to protect pregnant women from the harm of tobacco.

Ir-Doped Core-Shell Hollow Heterogeneous Nanospindles for Electrocatalytic Oxygen Evolution Reaction.

By utilizing Metal-organic framework (MOF) materials as a base, constructing electrocatalysts with heterogeneous structures offers advantages for catalyzing water splitting. In this study, a hollow heterogeneous nanocatalyst, Ir-MIL-88A@NiFe-LDHs, was prepared by growing a layered double hydroxides (LDHs) shell on MIL-88A substrate. The catalyst shows excellent oxygen evolution reaction (OER) performance in a 1.0 M KOH solution, requiring only 217 mV overpotential to achieve a current density of 10 mA cm-2 with a Tafel slope of 62.18 mV dec-1, indicating significant electrocatalytic performance and reaction kinetics characteristics. Furthermore, long-term OER testing also demonstrates the catalyst's outstanding stability. Emphasizing the interfacial interaction between MOF and LDHs, as well as the synergistic effect among Ni, Fe, and Ir elements, the study highlights how these factors collaboratively control the local electronic structure of the hollow Ir-MIL-88A@NiFe-LDHs, resulting in an efficient MOF-derived electrocatalyst.

An injectable hydrogel based on sodium alginate and gelatin treats bacterial keratitis through multimodal antibacterial strategy.

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.

Hydroxypropyl methylcellulose reinforced bilayer hydrogel dressings containing L-arginine-modified polyoxometalate nanoclusters to promote healing of chronic diabetic wounds.

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.

Association of systolic blood pressure variability with remote ischemic conditioning in acute ischemic stroke.

Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max-min: adjusted risk difference [RD] = 7.2, 95% CI 1.2-13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6-21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4-21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P < 0.05). No significant difference in SBPV parameters were found between treatment groups. This is the first report that Chinese patients with acute moderate ischemic stroke and presenting with higher SBPV, who were non-cardioemoblic stroke and not candidates for intravenous thrombolysis or endovascular therapy, would benefit more from RIC with respect to functional outcomes at 90 days, but 2-week RIC treatment has no effect on SBPV during hospital.