Characterization of HSP90 expression and function following CNS injury.

Spinal cord injury induces significant cellular stress responses. The Heat Shock Protein 90 (HSP90) plays a pivotal role as a molecular chaperone and is crucial for protein folding, stabilization, and cellular signaling pathways. Despite its important function in stress adaptation, the specific expression patterns and functional roles of HSP90 after nerve injury remain unclear. This study aimed to elucidate the expression dynamics and functional implications of HSP90 following central nervous system (CNS) injury. Using western blotting and immunohistochemical analyses, we observed upregulation of HSP90 expression in spinal cord tissues and within injured neurons in a spinal cord contusion injury model. Additionally, HSP90 was found to enhance neurite outgrowth in primary cortical neurons cultured in vitro. Furthermore, in a glutamate-induced neuronal injury model, the expression of HSP90 was up-regulated, and overexpression of HSP90 promoted neurite re-growth in damaged neurons. Overall, our findings highlight the critical involvement of HSP90 in the neural response to injury and offer valuable insights into potential therapeutic strategies for CNS repair.

Ras-Targeting Stabilized Peptide Increases Radiation Sensitivity of Cancer Cells.

Radiation therapy is one of the most common treatments for cancer. However, enhancing tumors' radiation sensitivity and overcoming tolerance remain a challenge. Previous studies have shown that the Ras signaling pathway directly influences tumor radiation sensitivity. Herein, we designed a series of Ras-targeting stabilized peptides, with satisfactory binding affinity (KD = 0.13 µM with HRas) and good cellular uptake. Peptide H5 inhibited downstream phosphorylation of ERK and increased radio-sensitivity in HeLa cells, resulting in significantly reduced clonogenic survival. The stabilized peptides, designed with an N-terminal nucleation strategy, acted as potential radio-sensitizers and broadened the applications of this kind of molecule. This is the first report of using stabilized peptides as radio-sensitizers, broadening the applications of this kind of molecule.

Statin administration or blocking PCSK9 alleviates airway hyperresponsiveness and lung fibrosis in high-fat diet-induced obese mice.

BACKGROUND: Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity. METHODS: Male C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-ß1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed. RESULTS: High-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-ß1, IL-1ß, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-ß1 over-expressed transgenic mice with normal diet. CONCLUSIONS: Lipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity.

Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study.

OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.

A study on the correlation between lung injury severity and cardiac function through a closed-loop model.

OBJECTIVE: Numerous clinical and pathological studies have confirmed that lung injury can cause cardiovascular disease, but there is no explanation for the mechanism by which the degree of lung injury affects cardiac function. We attempt to reveal this mechanism of influence by simulating a cyclic model. METHOD: This study established a closed-loop cardiovascular model with a series of electrical parameters. Including the heart, lungs, arteries, veins, etc., each part of the cardiovascular system is modeled using centralized parameters. Adjusting these lung resistances to alter the degree of lung injury is aimed at reflecting the impact of different degrees of lung injury on cardiac function. Finally, analyze and compare the changes in blood pressure, aortic flow, atrioventricular volume, and atrioventricular pressure among different lung injuries to obtain the changes in cardiac function. RESULTS: In this model, the peak aortic flow decreased, the earlier the trough appeared, and the total aortic flow decreased. Left atrial blood pressure decreased from 6.5 mmHg to around 5.5 mmHg, left ventricular blood pressure decreased from 100 mmHg to around 50 mmHg, and aortic blood pressure also decreased from 100 mmHg to around 50 mmHg. The blood pressure in the pulmonary artery, right atrium, and right ventricle increases. The right ventricular blood pressure decreased from 20 mmHg to around 40 mmHg, while the right atrial blood pressure slightly increased. It can be seen that the increase in impedance has a greater impact on ventricular blood pressure than on atrium. Pulmonary arterial pressure significantly increases, rising from 20 mmHg to around 50 mmHg, forming pulmonary hypertension. The left ventricular end-systolic potential energy, filling energy, stroke work, stroke output, left ventricular filling period, maximum blood pressure during ventricular ejection period, and stroke energy efficiency decrease. CONCLUSION: We established a closed-loop cardiovascular model that reveals that the more severe lung injury, the higher blood pressure in the pulmonary artery, right atrium, and right ventricle, while the lower blood pressure in the left atrium, left ventricle, and aorta. The increase in pulmonary impedance leads to abnormalities in myocardial contraction, diastolic function, and cardiac reserve capacity, leading to a decrease in cardiac function. This closed-loop model provides a method for pre assessment of cardiovascular disease after lung injury.

Spongia Sponges: Unabated Sources of Novel Secondary Metabolites.

Marine sponges of the genus Spongia have proven to be unabated sources of novel secondary metabolites with remarkable scaffold diversities and significant bioactivities. The discovery of chemical substances from Spongia sponges has continued to increase over the last few years. The current work provides an up-to-date literature survey and comprehensive insight into the reported metabolites from the members of the genus Spongia, as well as their structural features, biological activities, and structure-activity relationships when available. In this review, 222 metabolites are discussed based on published data from the period from mid-2015 to the beginning of 2024. The compounds are categorized into sesquiterpenes, diterpenes, sesterterpenes, meroterpenes, linear furanoterpenes, steroids, alkaloids, and other miscellaneous substances. The biological effects of these chemical compositions on a vast array of pharmacological assays including cytotoxic, anti-inflammatory, antibacterial, neuroprotective, protein tyrosine phosphatase 1B (PTP1B)-inhibitory, and phytoregulating activities are also presented.

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application.

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Bioactive metabolite profiles and quality of Rosa rugosa during its growing and flower-drying process.

Rosa rugosa is extensively cultivated in China for its remarkable fragrance and flavor, however, the metabolic changes in roses during growth and drying remain unclear. Our results revealed significant variations in phenol and flavonoid contents and antioxidant capacity in roses (Rosa rugosa f. plena (Regel) Byhouwer) under different conditions. Phenol contents were positively correlated with antioxidant capacity, with phytochemicals being most prominent in unfolded petals. The highest antioxidant capacity and phenol and flavonoid contents were observed in April. Considering their greater consumption value, whole flowers were more suitable than petals alone. Furthermore, considerable sensory and nutritional differences were observed in dried roses. Different drying methods increased their total phenol content of roses by 4.2-5.4 times and the antioxidant capacity by 2.9 times. Metabolomics revealed the altered contents of flavonoids, anthocyanins, lipids, amino acids, and saccharides. This study provides baseline data for the potential of roses as a natural source of antioxidants in the food and pharmaceutical industries.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Exploring the chemical diversity of sesquiterpenes from the rarely studied south China sea soft coral Sinularia tumulosa assisted by molecular networking strategy.

Molecular networking strategy-based prioritization of the isolation of the rarely studied soft coral Sinularia tumulosa yielded 14 sesquiterpenes. These isolated constituents consisted of nine different types of carbon frameworks, namely asteriscane, humulane, capillosane, seco-asteriscane, guaiane, dumortane, cadinane, farnesane, and benzofarnesane. Among them, situmulosaols A-C (1, 3 and 4) were previously undescribed ones, whose structures with absolute configurations were established by the combination of extensive spectral data analyses, quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory electronic circular dichroism calculations, the Snatzke's method, and the modified Mosher's method. Notably, situmulosaol C (4) was the second member of capillosane-type sesquiterpenes. The plausible biogenetic relationships of these skeletally different sesquiterpenes were proposed. All sesquiterpenoids were evaluated for their antibacterial, cytotoxic and anti-inflammatory effects. The bioassay results showed compound 14 exhibited significant antibacterial activities against a variety of fish and human pathogenic bacteria with MIC90 values ranging from 3.6 to 33.8 µg/mL. Moreover, moderate cytotoxic effects against HEL cells for components 13 and 14 and moderate inhibitory effect on lipopolysaccharide-induced inflammatory responses in RAW264.7 cells for substance 13 were also observed.

α-Glucosidase Inhibitory Phytochemical Components of Chinese Endemic Plant Whitfordiodendron filipes var. tomentosum.

Whitfordiodendron filipes var. tomentosum is an endemic plant in China. There have been no chemical or pharmacological studies of this plant reported before. In the current research, eight triterpenes and two steroids were obtained. Their structures were established by the analysis of NMR data and comparison with those reported in the literature. These ten structurally diverse compounds comprised five distinct carbon frameworks with different functionalities. The chemotaxonomic significance of these secondary metabolites was discussed, disclosing the common components between the variant W. filipes var. tomentosum and the species W. filipe. Evaluation of α-glucosidase inhibitory activities of these isolates disclosed that compounds 1, 2, 4, and 6 exhibited significant α-glucosidase inhibitory activities (IC50 = 16.6-19.2 µM), which were close in value to the positive control acarbose (IC50 = 11.5 µM). Moreover, the binding modes between the biologically active compounds 1, 2, 4, and 6 and the α-glucosidase protein were preliminarily studied using molecular docking. This study not only showed the chemical and biological profile of the plant W. filipes var. tomentosum but also revealed that these components could be developed as hypoglycemic lead compounds.

Full-Length Transcriptome Sequencing and RNA-Seq Analysis Offer Insights into Terpenoid Biosynthesis in Blumea balsamifera (L.) DC.

Blumea balsamifera (L.) DC., an important economic and medicinal herb, has a long history of being used as a traditional Chinese medicine. Its leaves have always been used as a raw material for the extraction of essential oils, comprising large amounts of terpenoids, which have good therapeutic effects on many diseases, such as eczema, bacterial infection, and hypertension. However, the genetic basis of terpenoid biosynthesis in this plant is virtually unknown on account of the lack of genomic data. Here, a combination of next-generation sequencing (NGS) and full-length transcriptome sequencing was applied to identify genes involved in terpenoid biosynthesis at five developmental stages. Then, the main components of essential oils in B. balsamifera were identified using GC-MS. Overall, 16 monoterpenoids and 20 sesquiterpenoids were identified and 333,860 CCS reads were generated, yielding 65,045 non-redundant transcripts. Among these highly accurate transcripts, 59,958 (92.18%) transcripts were successfully annotated using NR, eggNOG, Swissprot, KEGG, KOG, COG, Pfam, and GO databases. Finally, a total of 56 differently expressed genes (DEGs) involved in terpenoid biosynthesis were identified, including 38 terpenoid backbone genes and 18 TPSs, which provide a significant amount of genetic information for B. balsamifera. These results build a basis for resource protection, molecular breeding, and the metabolic engineering of this plant.

Deep Learning With Physics-Embedded Neural Network for Full Waveform Ultrasonic Brain Imaging.

The convenience, safety, and affordability of ultrasound imaging make it a vital non-invasive diagnostic technique for examining soft tissues. However, significant differences in acoustic impedance between the skull and soft tissues hinder the successful application of traditional ultrasound for brain imaging. In this study, we propose a physics-embedded neural network with deep learning based full waveform inversion (PEN-FWI), which can achieve reliable quantitative imaging of brain tissues. The network consists of two fundamental components: forward convolutional neural network (FCNN) and inversion sub-neural network (ISNN). The FCNN explores the nonlinear mapping relationship between the brain model and the wavefield, replacing the tedious wavefield calculation process based on the finite difference method. The ISNN implements the mapping from the wavefield to the model. PEN-FWI includes three iterative steps, each embedding the F CNN into the ISNN, ultimately achieving tomography from wavefield to brain models. Simulation and laboratory tests indicate that PEN-FWI can produce high-quality imaging of the skull and soft tissues, even starting from a homogeneous water model. PEN-FWI can achieve excellent imaging of clot models with constant uniform distribution of velocity, randomly Gaussian distribution of velocity, and irregularly shaped randomly distributed velocity. Robust differentiation can also be achieved for brain slices of various tissues and skulls, resulting in high-quality imaging. The imaging time for a horizontal cross-sectional imag e of the brain is only 1.13 seconds. This algorithm can effectively promote ultrasound-based brain tomography and provide feasible solutions in other fields.

Fast growth of single-crystal covalent organic frameworks for laboratory x-ray diffraction.

The imine-exchange strategy makes single-crystal growth of covalent organic frameworks (COFs) with large size (>15 microns) possible but is a time-consuming process (15 to 80 days) that has had limited success (six examples) and restricts structural characterization to synchrotron-radiation sources for x-ray diffraction studies. We developed a CF3COOH/CF3CH2NH2 protocol to harvest single-crystal COFs within 1 to 2 days with crystal sizes of up to 150 microns. The generality was exemplified by the feasible growth of 16 high-quality single-crystal COFs that were structurally determined by laboratory single-crystal x-ray diffraction with resolutions of up to 0.79 angstroms. The structures obtained included uncommon interpenetration of networks, and the details of the structural evolution of conformational isomers and host-guest interaction could be determined at the atomic level.

Plant and microbial response in constructed wetland treating tetracycline antibiotic polluted water: Evaluating the effects of microplastic size and concentration.

Microplastics (MPs) and antibiotics are novel water pollutants that have attracted increasing attention. Constructed wetlands (CWs) are widely applied treating various types of polluted water. How these two new pollutants affect plants and microorganisms in CWs, especially deciphering the unknown roles of MPs size and concentration, is of great essential. Here, five CW treatments with submerged macrophyte Myriophyllum aquaticum were established to treat oxytetracycline (OTC) antibiotic-polluted water. The effects of polystyrene (PS) nanoplastics (NPs) (700 nm) and MPs (90-110 µm) on plant and microbial communities at 10 µg/L and 1 mg/L, respectively, were systematically evaluated. PS reduced the nitrogen and phosphorus removal efficiencies and inhibited OTC removal. Low doses (10 µg/L) of NPs and high doses (1 mg/L) of MPs had the greatest effects on plant and microbial responses. The overall effect of MPs was greater than that of NPs. Compared with high NPs concentration (1 mg/L), low concentrations (10 µg/L) had higher catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) content. However, the activity and content of MPs at low concentrations (10 µg/L) were lower than those at high concentrations (1 mg/L). The coexistence of OTC and MPs/NPs decreased the microbial diversity and abundance. Low doses of NPs and high doses of MPs decreased the relative abundance of Abditibacteriota, Deinococccota, and Zixibacteria. Redundancy and network analyses revealed a strong correlation between pollutant removal and plant and microbial responses. NH4+-N and OTC removal was positively and negatively correlated with CAT, SOD, and MDA content, respectively. MDA positively correlated to chlorophyll content, whereas SOD showed a negative correlation with Chloroflexi. This study highlighted the scale effect of MPs in wastewater treatment via CWs. It enhances our understanding of the response of plants and microorganisms to the remediation of water co-polluted with MPs and antibiotics.

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing: an approach to regulating post-traumatic inflammation.

Impaired immunohomeostasis in diabetic wounds prolongs inflammation and cytokine dysfunction, thus, delaying or preventing wound-surface healing. Extensive clinical studies have been conducted on cytokine-induced killer (CIK) cells recently, as they can be easily proliferated using a straightforward, inexpensive protocol. Therefore, the function of CIK cells in regulating inflammatory environments has been drawing attention for clinical management. Throughout the current investigation, we discovered the regenerative capacity of these cells in the challenging environment of wounds that heal poorly due to diabetes. We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenvironment, promote vascularization and, ultimately, accelerate skin healing in diabetic mice. The results indicated that CIK cell treatment affects macrophage polarization and restores the function of regenerative cells under hyperglycemic conditions. This novel cellular therapy offers a promising intervention for clinical applications through specific inflammatory regulation functions.

Photo-controllable drug releasing bulk polyacrylic intraocular lens material for safer posterior capsular opacification prevention.

Posterior capsular opacification (PCO) is the most common complication that occurs after intraocular lens (IOL) implantation in cataract therapy. In recent years, IOLs have been developed as drug delivery platforms, but concerns over the safety of uncontrolled proliferative drug release have arisen. Therefore, a controlled drug release strategy is needed for safer PCO prevention. In this study, a new monomer contained coumarin group was introduced in material preparation, and poly(ethylene glycol phenyl ether methacrylate-co-2-(2-ethoxyethoxy) ethyl acrylate-co-7-(2-methacryloyloxyethoxy)-4-methylcoumarin) (PEEC) acrylic IOL materials were synthesized. The antiproliferative drug 5-fluorouracil (5-FU) could be chemically grafted to the PEEC IOL materials easily via a light induced [2 + 2] cycloaddition reaction with the coumarin group, getting drug-loaded IOL (PEEC@5-FU IOL). The PEEC@5-FU IOL exhibited excellent optical and mechanical properties and biocompatibility. More importantly, the loaded 5-FU could be easily controlled from release by light irradiation via photo-dissociation of the cyclobutane ring that was obtained by the [2 + 2] cycloaddition reaction of 5-FU and coumarin. The in vitro and in vivo experiments demonstrated that such photo-controllable drug release IOL could effectively prevent PCO after implantation in a safe way.