LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway.

Objective: To investigate the involvement of the homeobox gene B5 (HOXB5) in the progression and metastasis of osteosarcoma. Methods: The expression of HOXB5 in human osteosarcoma tissues and its correlation with clinical indicators were investigated using bioinformatics analysis and immunohistochemical labelling. Human osteosarcoma cells (HOS, MG63, U2OS, and Saos-2) and normal human osteoblasts (hFOB1.19) were cultivated. The expression of HOXB5 in these cells was detected using western blotting (WB) and RT‒PCR. Two cell lines exhibiting elevated HOXB5 expression were chosen and divided into three groups: the blank group (mock), control group (control) and transfection group (shHOXB5). The transfection group was infected with lentivirus expressing shRNAs targeting HOXB5. The transfection efficiency was detected by WB. Cell proliferation suppression was measured by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays; the percentage of apoptotic cells was determined by flow cytometry; and cell migration and invasion were detected via the Transwell chamber test. WB was utilized to determine the protein expression of genes linked to metastasis (MMP2, MMP9), apoptosis (Bax, Bcl-2), and the JAK2/STAT3 pathway (JAK2, p-JAK2, STAT3, p-STAT3). Results: In osteosarcoma tissues, HOXB5 expression was elevated and strongly correlated with distant metastasis. Silencing HOXB5 reduced the proliferation, migration and invasion of osteosarcoma cells; prevented the progression and metastasis of tumours in tumour-bearing nude mice; and reduced the activation of key proteins in the JAK2/STAT3 signalling pathway. Conclusion: Through the JAK2/STAT3 signalling pathway, HOXB5 plays a crucial role in the malignant progression of osteosarcoma and is a promising target for osteosarcoma treatment.

Sea Anemone-Inspired Slippery Liquid-Infused Porous Surface (SLIPS) with Bionic Cilia for Responsive 4D Antifouling.

The formation process of biofouling is actually a 4D process with both spatial and temporal dimensions. However, most traditional antifouling coatings, including slippery liquid-infused porous surface (SLIPS), are limited to performing antifouling process in the 2D coating plane. Herein, inspired by the defensive behavior of sea anemones' wielding toxic tentacles, a "4D SLIPS" (FSLIPS) is constructed with biomimetic cilia via a magnetic field self-assembly method for antifouling. The bionic cilia move in 3D space driven by an external magnetic field, thereby preventing the attachment of microorganisms. The FSLIPS releases the gaseous antifoulant (nitric oxide) at 1D time in response to light, thereby achieving a controllable biocide effect on microorganisms. The FSLIPS regulates the movement of cilia via the external magnetic field, and controls the release of NO overtime via the light response, so as to adjust the antifouling modes on demand during the day or night. The light/magnetic response mechanism endow the FSLIPS with the ability to adjust the antifouling effect in the 4D dimension of 1D time and 3D space, effectively realizing the intelligence, multi-dimensionality and precision of the antifouling process.

Self-Healing Polyurethane Elastomers with Superior Tensile Strength and Elastic Recovery Based on Dynamic Oxime-Carbamate and Hydrogen Bond Interactions.

The preparation of self-healing polyurethane elastomers (PUEs) incorporating dynamic bonds is of considerable practical significance. However, developing a PUE with outstanding mechanical properties and high self-healing efficiency poses a significant challenge. Herein, this work has successfully developed a series of self-healing PUEs with various outstanding properties through rational molecular design. These PUEs incorporate m-xylylene diisocyanate and reversible dimethylglyoxime as hard segment, along with polytetramethylene ether glycol as soft segment. A significant amount of dynamic oxime-carbamate and hydrogen bonds are formed in hard segment. The microphase separated structure of the PUEs enables them to be colorless with a transparency of >90%. Owing to the chemical composition and multiple dynamic interactions, the PUEs are endowed with ultra-high tensile strength of 34.5 MPa, satisfactory toughness of 53.9 MJ m-3, and great elastic recovery both at low and high strains. The movement of polymer molecular chains and the dynamic reversible interactions render a self-healing efficiency of 101% at 70 °C. In addition, this self-healing polyurethane could still maintain high mechanical properties after recycling. This study provides a design strategy for the preparation of a comprehensive polyurethane with superior overall performance, which holds wide application prospects in the fields of flexible displays and solar cells.

Bioinspired axial S-coordinated single-atom cobalt catalyst to efficient activate peroxymonosulfate for selective high-valent Co-Oxo species generation.

The efficient activation and selective high-valent metal-oxo (HVMO) species generation remain challenging for peroxymonosulfate (PMS)-based advanced oxidation processes (PMS-AOPs) in water purification. The underlying mechanism of the activation pathway is ambiguous, leading to a massive dilemma in the control and regulation of HVMO species generation. Herein, bioinspired by the bio-oxidase structure of cytochrome P450, the axial coordination strategy was adopted to tailor a single-atom cobalt catalyst (CoN4S-CB) with an axial S coordination. CoN4S-CB high-selectively generated high-valent Co-Oxo species (Co(IV)=O) via PMS activation. Co(IV)=O demonstrated an ingenious oxygen atom transfer (OAT) reaction to achieve the efficient degradation of sulfamethoxazole (SMX), and this allowed robust operation in various complex environments. The axial S coordination modulated the 3d orbital electron distribution of the Co atom. Density functional theory (DFT) calculation revealed that the axial S coordination decreased the energy barrier for PMS desorption and lowered the free energy change (ΔG) for Co(IV)=O generation. CoN4S-PMS* had a narrow d-band close to the Fermi level, which enhanced charge transfer to accelerate the cleavage of O-O and O-H bonds in PMS. This work provides a broader perspective on the activator design with natural enzyme structure-like active sites to efficient activate PMS for selective HVMO species generation.

A Tape-Wrapping Strategy towards Electrochemical Fabrication of Water-Dispersible Graphene.

Graphene has achieved mass production via various preparative routes and demonstrated its uniqueness in many application fields for its intrinsically high electron mobility and thermal conductivity. However, graphene faces limitations in assembling macroscopic structures because of its hydrophobic property. Therefore, balancing high crystal quality and good aqueous dispersibility is of great importance in practical applications. Herein, we propose a tape-wrapping strategy to electrochemically fabricate water-dispersible graphene (w-Gr) with both excellent dispersibility (~4.5 mg/mL, stable over 2 months), and well-preserved crystalline structure. A large production rate (4.5 mg/min, six times faster than previous electrochemical methods), high yield (65.4% ≤5 atomic layers) and good processability are demonstrated. A mechanism investigation indicates that the rational design of anode configuration to ensure proper oxidation, deep exfoliation and unobstructed mass transfer is responsible for the high efficiency of this strategy. This simple yet efficient electrochemical method is expected to promote the scalable preparation and applications of graphene.

Submerged macrophyte restoration enhanced microbial carbon utilization in shallow lakes.

Submerged macrophytes are integral to the functioning of shallow lakes through their interaction with microorganisms. However, we have a limited understanding of how microbial communities in shallow lakes respond when macrophytes are restored after being historically extirpated. Here, we explored the interactions between prokaryotic communities and carbon utilization in two lakes where submerged macrophytes were restored. We found restoration reduced total carbon in sediment by 8.9 %-27.9 % and total organic carbon by 16.7 %-36.9 % relative to control treatment, but had no effects on carbon content in the overlying water. Sediment microbial communities were more sensitive to restoration than planktonic microbes and showed enhanced utilization of simple carbon substrates, such as Tween 40, after restoration. The increase in carbon utilization was attributed to declines in the relative abundance of some genera, such as Saccharicenans and Desertimonas, which were found weakly associated with the utilization of different carbon substrates. These genera likely competed with microbes with high carbon utilization in restored areas, such as Lubomirskia. Our findings highlight how restoring submerged macrophytes can enhance microbial carbon utilization and provide guidance to improve the carbon sequestration capacity of restored shallow lakes.

Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

Microbial phosphorus-cycling genes in soil under global change.

The ongoing climate change on the Tibetan Plateau, leading to warming and precipitation anomalies, modifies phosphorus (P) cycling in alpine meadow soils. However, the interactions and cascading effects of warming and precipitation changes on the key "extracellular" and "intracellular" P cycling genes (PCGs) of bacteria are largely unknown for these P-limited ecosystems. We used metagenomics to analyze the individual and combined effects of warming and altered precipitation on soil PCGs and P transformation in a manipulation experiment. Warming and increased precipitation raised Olsen-P (bioavailable P, AP) by 13% and 20%, respectively, mainly caused by augmented hydrolysis of organic P compounds (NaOH-Po). The decreased precipitation reduced soil AP by 5.3%. The richness and abundance of the PCGs' community in soils on the cold Tibetan plateau were more sensitive to warming than altered precipitation. The abundance of PCGs and P cycling processes decreased under the influence of individual climate change factors (i.e., warming and altered precipitation alone), except for the warming combined with increased precipitation. Pyruvate metabolism, phosphotransferase system, oxidative phosphorylation, and purine metabolism (all "intracellular" PCG) were closely correlated with P pools under climate change conditions. Specifically, warming recruited bacteria with the phoD and phoX genes, which encode enzymes responsible for phosphoester hydrolysis (extracellular P cycling), strongly accelerated organic P mineralization and so, directly impacted P bioavailability in alpine soil. The interactions between warming and altered precipitation profoundly influenced the PCGs' community and facilitated microbial adaptation to these environmental changes. Warming combined with increased precipitation compensated for the detrimental impacts of the individual climate change factors on PCGs. In conclusion, warming combined with rising precipitation has boosting effect on most P-related functions, leading to the acceleration of P cycling within microbial cells and extracellularly, including mineralization and more available P release for microorganisms and plants in alpine soils.

Shear damage mechanisms of jointed rock mass: a macroscopic and mesoscopic study.

The joints are existing throughout the underground rock mass. It is of great significance to investigate the shear performance of the rock mass to maintain the stability of the underground structure. In this study, we conducted orthogonal tests to determine the proportion of rock-like materials, and used JRC curves to make specimen molds and then prepare the specimens. We conducted straight shear tests and uniaxial compression tests to determine the various mechanical parameters of the rock-like materials. Next, we carried out the compression and shear tests to investigate the shear characteristics of the specimens, and study the damage pattern and shear strength of the jointed rock mass under different confining pressures and roughness levels. The mesoscopic displacements in the shear process of joints were analyzed by using ABAQUS. The test results show that the effect of the confining pressure on the shear strength of the joint plane is relatively obvious, and a larger confining pressure indicates a larger shear strength. The effects of different joint plane roughness and shear rated on the shear characteristics of the joint plane are also significant. The mesoscopic displacement difference inside the joint plane with higher roughness is relatively large, and the stress concentration phenomenon is obvious and lasts longer, which leads to the faster destruction of the specimen with higher roughness and the higher destruction degree. Therefore, we suggest that the priority should be given to the reinforcement of jointed rock mass with high roughness during the construction to prevent sudden destabilization and failure.

Therapeutic potential of natural products and underlying targets for the treatment of aortic aneurysm.

Aortic aneurysm is a vascular disease characterized by irreversible vasodilatation that can lead to dissection and rupture of the aortic aneurysm, a life-threatening condition. Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are two main types. The typical treatments for aortic aneurysms are open surgery and endovascular aortic repair, which are only indicated for more severe patients. Most patients with aneurysms have an insidious onset and slow progression, and there are no effective drugs to treat this stage. The inability of current animal models to perfectly simulate all the pathophysiological states of human aneurysms may be the key to this issue. Therefore, elucidating the molecular mechanisms of this disease, finding new therapeutic targets, and developing effective drugs to inhibit the development of aneurysms are the main issues of current research. Natural products have been applied for thousands of years to treat cardiovascular disease (CVD) in China and other Asian countries. In recent years, natural products have combined multi-omics, computational biology, and integrated pharmacology to accurately analyze drug components and targets. Therefore, the multi-component and multi-target complexity of natural products have made them a potentially ideal treatment for multifactorial diseases such as aortic aneurysms. Natural products have regained popularity worldwide. This review provides an overview of the known natural products for the treatment of TAA and AAA and searches for potential cardiovascular-targeted natural products that may treat TAA and AAA based on various cellular molecular mechanisms associated with aneurysm development.

Study on the transformation of nitrate nitrogen by manganese-catalyzed iron-carbon micro-electrolysis and microbial coupling.

Nitrate-nitrogen pertains to the nitrogen component of the overall nitrate present in a given sample in order to reduce nitrate nitrogen pollution in water, nitrate nitrogen removal methods based on iron-carbon micro-electrolysis have become a key research focus. The process and mechanism of nitrate nitrogen removal by microbial coupling was comprehensively explored in a novel iron-carbon micro-electrolysis (ICME) system. In order to establish the transformation pathway of nitrate nitrogen in water, the transformation paths of nitrate nitrogen in water before and after coupling microorganisms in three groups of continuous flow reaction devices, namely sponge iron (s-Fe0), sponge iron + biochar (s-Fe0/BC) and sponge iron + biochar + manganese sand (s-Fe0/BC/MS), were studied. The morphology and composition changes of sponge iron were analyzed by means of characterization, and the microbial population changes in the three groups were analyzed by high-throughput sequencing. Results showed that the nitrate conversion rate in the s-Fe0, s-Fe0/BC and s-Fe0/BC/MS systems reached 99.48%, 99.57% and 99.36%, respectively, with corresponding ammonia nitrogen generation, rates of 3.77%, 9.34% and 11.24% and nitrogen generation rates of 95.71%, 90.23% and 88.12%. Scanning electron microscopy imaging showed that in the s-Fe0/BC and s-Fe0/BC/MS systems the surface of sponge iron was highly corroded, with granular substances in the corrosion product clusters. X-ray photoelectron spectroscopy analysis found that the relative contents of Fe2O3 in the surface oxides of sponge iron after microbial coupling were 38.02% and 71.27% in the s-Fe0/BC and s-Fe0/BC/MS systems, while the relative Fe3O4 contents were 61.98% and 28.72%, respectively. Microbial high-throughput sequencing analysis revealed that the Chao and Ace index values in the s-Fe0 system were 871.89 and 880.78, while in the s-Fe0/BC system they were 1012.05 and 1017.29, and in the s-Fe0/BC/MS system were 1241.09 and 1198.29, respectively. The relative proportion of Thauera in the s-Fe0, s-Fe0/BC, and s-Fe0/BC/MS systems was 16.76%,14.25% and 10.01%, while the proportion of Acetoanaerobium was 15.36%, 13.27% and 11.11%, and the proportion of Chloroflexi was 0%, 1.11% and 2.18%, respectively. Furthermore, FAPROTAX function annotation found that the expression levels of chemoheterotrophs in the s-Fe0, s-Fe0/BC and s-Fe0/BC/MS systems were 43 316 OTU, 37 289 OTU and 34 205 OTU, while nitrate respiration expression levels were 16 230 OTU, 15 483 OTU and 9149 OTU, with nitrogen respiration expression levels of 16 328 OTU, 15 493 OTU and 9154 OTU, respectively. These findings suggest that nitrate is converted into nitrogen gas and ammonia nitrogen through the actions of the coupled system of sponge iron/biochar/manganese sand and microorganisms. The catalytic effect of MnO2 promotes the conversion of Fe2+ to Fe3+, generating more electrons, allowing denitrifying bacteria to reduce more nitrate nitrogen, effectively coupling the manganese-catalyzed ICME reaction and microbial denitrification. The micro-electrolysis system and the addition of manganese sand enhanced biodiversity within the s-Fe0/BC/MS system. The heterotrophic bacteria Thauera and Acetoanaerobium were the dominant microorganisms in all three systems, although the micro-electrolysis system with added manganese sand significantly reduced the proportion of facultative bacteria Thauera and Acetoanaerobium and promoted the growth of autotrophic Chloroflexi bacteria. The ecological functions of the three systems were mainly nitrate respiration and nitrogen respiration. By comparing the expression levels of nitrate respiration and nitrogen respiration in s-Fe0/BC and s-Fe0/BC/MS systems, it can be seen that the addition of manganese sand reduced microbial activity.

Discovery of the Highly Selective and Potent STAT3 Inhibitor for Pancreatic Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, and for full activation of STAT3, the cooperative phosphorylation of both tyrosine 705 (Tyr705) and serine 727 (Ser727) is needed. Further, a selective inhibitor of STAT3 dual phosphorylation has not been developed. Here, we identified a low nanomolar potency and highly selective small-molecule STAT3 inhibitor that simultaneously inhibits both STAT3 Tyr705 and Ser727 phosphorylation. YY002 potently inhibited STAT3-dependent tumor cell growth in vitro and achieved potent suppression of tumor growth and metastasis in vivo. More importantly, YY002 exhibited favorable pharmacokinetics, an acceptable safety profile, and superior antitumor efficacy compared to BBI608 (STAT3 inhibitor that has advanced into phase III trials). For the mechanism, YY002 is selectively bound to the STAT3 Src Homology 2 (SH2) domain over other STAT members, which strongly suppressed STAT3 nuclear and mitochondrial functions in STAT3-dependent cells. Collectively, this study suggests the potential of small-molecule STAT3 inhibitors as possible anticancer therapeutic agents.

Coupling of biogas residue biochar and low-magnitude electric fields promotes anaerobic co-digestion of sewage sludge and food waste.

Biochar-assisted anaerobic digestion (AD) remains constrained due to the inefficient decomposition of complex organics, even with the direct interspecies electron transfer (DIET) pathway. The coupling of electrochemistry with the anaerobic biological treatment could shorten lengthy retention time in co-digestion by improving electron transfer rates and inducing functional microbial acclimation. Thus, this work investigated the potential of improving the performance of AD by coupling low-magnitude electric fields with biochar derived from the anaerobically digested biogas residue. Different voltages (0.3, 0.6, and 0.9 V) were applied at various stages to assess the impact on biochar-assisted AD. The results indicate that an external voltage of 0.3 V, coupled with 5 g/L of biochar, elevates CH4 yield by 45.5% compared to biogas residue biochar alone, and the coupled approach increased biogas production by up to 143% within 10 days. This finding may be partly explained by the enhanced utilization of substrates and the increased amounts of specific methanogens such as Methanobacterium and Methanosarcina. The abundance of the former increased from 4.0 to 11.3%, which enhances the DIET between microorganisms. Furthermore, the coupling method shows better potential for enhancing AD compared to preparing iron-based biochar, and these results present potential avenues for its broader applications.

The melanin pigment gene black mediates body pigmentation and courtship behaviour in the German cockroach Blattella germanica.

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

Neighboring Effects of Sulfur Oxidation State on Dynamic Covalent Bonds and Assemblies.

The impact of a varied sulfur oxidation state (sulfide, sulfoxide, and sulfone) on imine dynamic covalent chemistry is presented. The role of noncovalent interactions, including chalcogen bonds and CH hydrogen bonds, on aldehyde/imine structures and imine exchange reactions was elucidated through experimental and computational evidence. The change in the sulfur oxidation state and diamine linkage further allowed the regulation of imine macrocycles, providing a platform for controlling molecular assemblies.

Marine sulfated glycans inhibit the interaction of heparin with S-protein of SARS-CoV-2 Omicron XBB variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans. As with many other viruses, SARS­CoV­2 utilizes heparan sulfate (HS) glycosaminoglycan (GAG) on the surface of host cells to facilitate viral attachment and initiate cellular entry through the ACE2 receptor. Therefore, interfering with virion-HS interactions represents a promising target to develop broad-spectrum antiviral therapeutics. Sulfated glycans derived from marine organisms have been proven to be exceptional reservoirs of naturally existing HS mimetics, which exhibit remarkable therapeutic properties encompassing antiviral/microbial, antitumor, anticoagulant, and anti-inflammatory activities. In the current study, the interactions between the receptor-binding domain (RBD) of S-protein of SARS-CoV-2 (both WT and XBB.1.5 variants) and heparin were applied to assess the inhibitory activity of 10 marine-sourced glycans including three sulfated fucans, three fucosylated chondroitin sulfates and two fucoidans derived from sea cucumbers, sea urchin and seaweed Saccharina japonica, respectively. The inhibitory activity of these marine derived sulfated glycans on the interactions between RBD of S-protein and heparin was evaluated using Surface Plasmon Resonance (SPR). The RBDs of S-proteins from both Omicrion XBB.1.5 and wild-type (WT) were found to bind to heparin, which is a highly sulfated form of HS. All the tested marine-sourced sulfated glycans exhibited strong inhibition of WT and XBB.1.5 S-protein binding to heparin. We believe the study on the molecular interactions between S-proteins and host cell glycosaminoglycans provides valuable insight for the development of marine-sourced, glycan-based inhibitors as potential anti-SARS-CoV-2 agents.

Innovative insights: ITLN1 modulates renal injury in response to radiation.

Radiation-induced kidney injury is a common side effect of radiotherapy, as the pelvic region is in close proximity to the kidneys, posing a risk of inducing radiation-induced kidney injury when treating any pelvic malignancies with radiotherapy. This type of injury typically manifests as chronic kidney disease a few months after radiotherapy, with the potential to progress to end-stage renal disease. Radiation-induced damage involves various components of the kidney, including glomeruli, tubules, interstitium, and extracellular matrix. Therefore, investigating its molecular mechanisms is crucial. In this study, we extensively searched literature databases, selecting recent transcriptomic studies related to acute kidney injury (AKI) published in the past decade. We downloaded the raw RNA sequencing datasets GSE30718 and GSE66494 related to AKI from the GEO database and identified that intestinal-type lectin ITLN1 plays a significant role in regulating radiation-induced kidney injury in rats. Differential gene analysis was performed using chip data from the GEO database, and further bioinformatics analysis identified 13 genes that may be involved in regulating kidney injury, with ITLN1 being the most relevant to kidney damage, thus selected as the target gene for this study. Subsequently, a rat model of radiation-induced kidney injury was established for experimental validation, assessing kidney tissue morphology and injury extent through staining observation and immunohistochemical staining. The protective effect of ITLN1 on kidney function was evaluated by measuring changes in rat body weight and blood pressure, serum kidney injury markers, and kidney structure. The experimental results indicate that overexpression of ITLN1 can improve kidney function in rats with radiation-induced kidney injury by activating the Akt/GSK-3ß/Nrf2 signaling pathway, suppressing oxidative stress, cell apoptosis, inflammation, cellular senescence, and fibrosis. This study highlights the significant role of ITLN1 in regulating kidney injury, providing a novel target for future treatments of radiation-induced kidney injury.

Bubble Growth on Hydrophobic Rough Surfaces in the Shear Flow.

It is well known that bubbles will form on a hydrophobic rough surface immersed in water, which can create a surface covered with bubbles and leads to drag reduction. However, it is still not clear how bubbles grow on the surface under flow conditions. In this work, a rotating flow field is created using a parallel-plate setup of a rotational rheometer, and sample surfaces with different roughnesses and wettabilities are examined with different shear rates. The growth of bubbles is exclusively observed on the hydrophobic rough surface, and subsequent drag reduction is also detected simultaneously. The growth of bubbles is attributed to heterogeneous nucleation in the crevices under a local pressure reduction generated by the shear flow. A geometric model is established to describe the profile evolution of the trapped bubble in the crevice based on the contact angle and the pressure balance across the gas-liquid interface, which involves the variations of the Laplace pressure resulting from changes in the local liquid pressure. The growth of bubbles on the hydrophobic rough surface does not need a large decrease of the surrounding pressure or a high moving speed, which will have potential applications in drag reduction under the condition of a moderate shear rate.