Synergistic engineering of heterostructure and oxygen vacancy in cobalt hydroxide/aluminum oxyhydroxide as bifunctional electrocatalysts for urea-assisted hydrogen production.

Designing inexpensive, high-efficiency and durable bifunctional catalysts for urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) is an encouraging tactic to produce hydrogen with reduced energy expenditure. Herein, oxygen vacancy-rich cobalt hydroxide/aluminum oxyhydroxide heterostructure on nickel foam (denoted as Co(OH)2/AlOOH/NF-100) has been fabricated using one step hydrothermal process. Theoretical calculation and experimental results indicate the electrons transfer from Co(OH)2 to highly active AlOOH results in the interfacial charge redistribution and optimization of electronic structure. Abundant oxygen vacancies in the heterostructure could improve the conductivity and simultaneously serve as the active sites for catalytic reaction. Consequently, the optimal Co(OH)2/AlOOH/NF-100 demonstrates excellent electrocatalytic performance for HER (62.9 mV@10 mA cm-2) and UOR (1.36 V@10 mA cm-2) due to the synergy between heterointerface and oxygen vacancies. Additionally, the in situ electrochemical impedance spectrum (EIS) for UOR suggests that the heterostructured catalyst exhibits rapid reaction kinetics, mass transfer and current response. Importantly, the urea-assisted electrolysis composed of the Co(OH)2/AlOOH/NF-100 manifests a low cell voltage (1.48 V @ 10 mA cm-2) in 1 M KOH containing 0.5 M urea. This work presents a promising avenue to the development of HER/UOR bifunctional electrocatalysts.

Review of molecular dynamics simulations in laser-based micro/nano-fabrication.

Laser technology is integral to the advancement of micro/nano-fabrication. While laser machining offers numerous advantages over alternative micro/nano-fabrication techniques, several challenges and bottlenecks continue to impede its large-scale industrial implementation. In response to these constraints, the molecular dynamics (MD) method has emerged as a formidable tool for optimizing the process parameters of laser micro/nano-fabrication and investigating alternative laser-based micro/nano-fabrication techniques. In this review, the application of MD in laser-based micro/nano-fabrication is comprehensively examined, including numerical simulations of short-pulse, long-pulse, continued laser and hybrid laser machining. The corresponding MD simulation schemes for lasers with different pulse widths are outlined. The mechanisms of laser-material interactions across diverse processing scenarios and the complete process of laser-based micro/nano-fabrication are also elucidated. Furthermore, the prevailing challenges in this domain and potential solutions are discussed, with future research directions being charted based on current knowledge and technological advancements.

Mitigating Adverse Effects of Cu-containing Intrauterine Devices Using A Highly Biocompatible Cu-5Fe alloy.

Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu2+. To minimize the burst release, in this study, we designed a series of Cu-Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu-Fe alloys and UFG Cu-Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and in vitro cytotoxicity. With careful comparison and selection, we chose the CG Cu-5Fe and UFG Cu-5Fe for in vivo tests using rat model, including tissue biocompatibility, in vivo corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu-5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu-5Fe alloys exhibited dramatic suppression of Cu2+ release in simulated uterine fluid for the long-term immersion process. The in vivo tissue compatibility was significantly improved with both CG and UFG Cu-5Fe alloys implanted in the rats' uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu-5Fe alloys can be the promising candidate material for Cu-IUD. STATEMENT OF SIGNIFICANCE: A highly biocompatible Cu-Fe alloy was designed and fabricated for Cu-containing intrauterine devices (Cu-IUD). With 5wt% Fe, the burst release of Cu2+ is inhibited due to the formed galvanic cell of Cu and Fe, resulting in earlier release of Fe3+. As Fe is the most abundant essential trace element of human body, it can mitigate the toxic effects of Cu2+, thus significantly improving both in vitro cell compatibility and in vivo tissue compatibility. More importantly, the Cu-5Fe alloy exhibits 100% contraceptive efficiency as the CG Cu, but with greatly reduced adverse effects to the uterus tissues. An advanced Cu-IUD can be developed using Cu-Fe alloys.

Soluble inorganic quantum dots as an electrolyte additive to boost lithium-sulfur battery performance.

Herein, MoS2 quantum dots (QDs) are constructed to serve as electrolyte additives for lithium-sulfur batteries, which can 'solidify' soluble polysulfides by chemisorption and promote sulfur conversion chemistry by electrocatalysis. The Li-S cell with MoS2 QDs shows high retained capacity and high-rate capability, much better than the counterpart without MoS2 QDs.

Patient-specific finite element analysis of four different fixation methods for transversely unstable radial head fractures.

Plate fixation is a common treatment option for radial head fractures (RHFs). Due to the benefits of less invasiveness and fewer complications of internal fixation, the application of small-diameter headless compression screws (HCSs) to treat RHFs has become a new trend. This study aimed to compare the mechanical stability of four distinct internal fixation protocols for transversely unstable RHFs via finite element analysis. Using computed tomography data from 10 patients, we developed 40 patient-specific FE models of transversely unstable RHFs fixed by parallel, crossed, and tripod HCSs and mini-T plate (MTP). Under simulated physiological loading of the elbow joint, the construct stiffness, displacement, and von Mises stresses were evaluated and verified by a biomechanical experiment. Under shear loading, the MTP group exhibited lower construct stiffness, larger displacement, and higher Von Mises stress than the HCSs group. The stiffness of tripod HCSs was greater than parallel and crossed screw fixation techniques. There was a strong relationship between apparent bone density and construct stiffness (R = 0.98 to 0.99). In the treatment of transversely unstable RHFs, HCSs have superior biomechanical stability than MTP. The tripod technique was also more stable than parallel and crossed fixation.

Developing an enhanced chimeric permuted intron-exon system for circular RNA therapeutics.

Rationale: Circular RNA (circRNA) therapeutics hold great promise as an iteration strategy in messenger RNA (mRNA) therapeutics due to their inherent stability and durable protein translation capability. Nevertheless, the efficiency of RNA circularization remains a significant constraint, particularly in establishing large-scale manufacturing processes for producing highly purified circRNAs. Hence, it is imperative to develop a universal and more efficient RNA circularization system when considering synthetic circRNAs as therapeutic agents with prospective clinical applications. Methods: We initially developed a chimeric RNA circularization system based on the original permuted intron-exon (PIE) and subsequently established a high-performance liquid chromatography (HPLC) method to obtain highly purified circRNAs. We then evaluated their translational ability and immunogenicity. The circRNAs expressing human papillomavirus (HPV) E7 peptide (43-62aa) and dimerized receptor binding domain (dRBD) from SARS-CoV-2 were encapsulated within lipid nanoparticles (LNPs) as vaccines, followed by an assessment of the in vivo efficacy through determination of antigen-specific T and B cell responses, respectively. Results: We have successfully developed a universal chimeric permuted intron-exon system (CPIE) through engineering of group I self-splicing introns derived from Anabaena pre-tRNALeu or T4 phage thymidylate (Td) synthase gene. Within CPIE, we have effectively enhanced RNA circularization efficiency. By utilizing size exclusion chromatography, circRNAs were effectively separated, which exhibit low immunogenicity and sustained potent protein expression property. In vivo data demonstrate that the constructed circRNA vaccines can elicit robust immune activation (B cell and/or T cell responses) against tumor or SARS-CoV-2 and its variants in mouse models. Conclusions: Overall, we provide an efficient and universal system to synthesize circRNA in vitro, which has extensive application prospect for circRNA therapeutics.

VSIG4 induces the immunosuppressive microenvironment by promoting the infiltration of M2 macrophage and Tregs in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has a poor prognosis. Despite the impressive advancements in treating ccRCC using immune checkpoint (IC) blockade, such as PD-1/PD-L1 inhibitors, a considerable number of ccRCC patients experience adaptive resistance. Therefore, exploring new targetable ICs will provide additional treatment options for ccRCC patients. We comprehensively analyzed multi-omics data and performed functional experiments, such as pathologic review, bulk transcriptome data, single-cell sequencing data, Western blotting, immunohistochemistry and in vitro/in vivo experiments, to explore novel immunotherapeutic targets in ccRCC. It was found that immune-related genes VSIG4, SAA1, CD7, FOXP3, IL21, TNFSF13B, BATF, CD72, MZB1, LTB, CCL25 and KLRK1 were significantly upregulated in ccRCC (Student's t test and p-value < 0.05; 36 normal and 267 ccRCC tissues in raining cohort; 36 normal and 266 ccRCC tissues in validation cohort) and correlated with the poor prognosis of ccRCC patients (Wald test and p-value < 0.05 in univariate cox analysis; log-rank test and p-value < 0.05 in Kaplan-Meier method; 267 patients in training cohort and 266 in validation cohort). In particular, we found the novel IC target VSIG4 was specifically expressed in inhibitory immune cells M2-biased tumor-associated macrophages (TAMs), conventional dendritic cell 2 (cDC2) cells, and cycling myeloid cells in ccRCC microenvironment. Moreover, VSIG4 showed a closely relation with resistance of Ipilimumab/Nivolumab immunotherapy in ccRCC. Furthermore, VSIG4 promoted the infiltration of M2 macrophages, Tregs, and cDC2 in ccRCC tissues. VSIG4+ TAMs and VSIG4+ cDC2s may be a kind of immune cell subtypes related to immunosuppression. VSIG4 may play similar roles with other IC ligands, as it is highly expressed on the surface of antigen-presenting cells and ccRCC cells to inhibit T cells activity and facilitate immune escape. Targeting IC gene VSIG4 may provide a novel immunotherapeutic strategy to ccRCC patients with resistance to existing targeted therapy options.

Grain Boundary Filling Empowers (002)-Textured Zn Metal Anodes with Superior Stability.

Aqueous Zn battery is promising for grid-level energy storage due to its high safety and low cost, but dendrite growth and side reactions at the Zn metal anode hinder its development. Designing Zn with (002) orientation improves the stability of the Zn anode, yet grain boundaries remain susceptible to corrosion and dendrite growth. Addressing these intergranular issues is crucial for enhancing the electrochemical performance of (002)-textured Zn. Here, a strategy based on grain boundary wetting to fill intergranular regions and mitigate these issues is reported. By systematically investigating boundary fillers and filling conditions, In metal is chosen as the filler, and one-step annealing is used to synergistically convert commercial Zn foils into single (002)-textured Zn while filling In into the boundaries. The inter-crystalline-modified (002)-textured Zn (IM(002) Zn) effectively inhibits corrosion and dendrite growth, resulting in excellent stability in batteries. This work offers new insights into Zn anode protection and the development of high-energy Zn batteries.

The relationship between sarcopenia and related bioindicators and changes after intensive lifestyle intervention in elderly East-China populations.

BACKGROUND: As populations live longer, there is a progressive increase in chronic degenerative diseases, particularly those related to the musculoskeletal system. Sarcopenia is characterized by loss of skeletal muscle mass, muscle strength, and loss of physical function. It is a common disease in older adults associated with various adverse health outcomes. There is a lack of bioindicators to screen for sarcopenia. Albumin and lymphocyte counts are commonly used to assess the degree of malnutrition, and blood routine, lipids, and thyroid function are relatively easy to obtain as part of a routine physical examination. Therefore, finding blood markers that can screen for sarcopenia is essential. Our primary aim was to explore whether the bioindicators of body composition, lymphocytes, albumin, lipids, and thyroid hormones are associated with sarcopenia, and a secondary aim was to investigate changes in these indicators after an intensive lifestyle intervention preliminarily. METHODS: 60 subjects were selected from Runda and Bailian community health centers in Suzhou, China. They underwent body composition analysis and tested lymphocyte, albumin, lipid, and thyroid hormone levels. The 30 sarcopenia subjects underwent a 3-month intensive lifestyle intervention program. At the end of the intervention, we rechecked the bioindicators. Statistical analyses were performed in IBM SPSS v26.0. RESULTS: The blood indices of sarcopenia subjects were generally lower in albumin, non-high-density lipoprotein cholesterol (non-HDL-C), and free triiodothyronine (FT3). Body mass index (BMI)(r = 0.6266, p < 0.0001), fat-free mass (r = 0.8110, p < 0.0001), basal metabolism (r = 0.7782, p < 0.0001), and fat mass (r = 0.3916, p = 0.0020) were positively correlated with appendicular skeletal muscle index (ASMI). Higher BMI and FT3 were associated with lower odds of sarcopenia, while higher fat mass was associated with higher odds of sarcopenia. After a 3-month intensive intervention, sarcopenia subjects had a significant increase in BMI, ASMI, lymphocyte, and albumin levels, and an increase in FT3, but with a non-significant difference (p = 0.342). CONCLUSIONS: Low BMI, FT3, and high fat mass were associated with sarcopenia. Intensive lifestyle intervention can significantly improve ASMI, BMI, lymphocytes, albumin, and FT3 in sarcopenia subjects, which is favorable for delaying the progression of sarcopenia. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov, registration number NCT06128577, date of registration: 07/11/2023.

Injectable polypeptide-polysaccharide depot for preventing postoperative tumor recurrence by concurrent in situ chemotherapy and brachytherapy.

Chemotherapy and radiotherapy in combination with sequence regimens are recognized as the current major strategy for suppressing postoperative tumor recurrence. However, systemic side effects and poor in-field cooperation of the two therapies seriously impair the therapeutic efficacy of patients. The combination of brachytherapy and chemotherapy through innovative biomaterials has proven to be an important strategy to achieve synergistic effects of radiotherapy and chemotherapy in-time and in-field. However, for postoperative chemoradiotherapy, as far as we know, there are few relevant reports. Herein, an injectable pH-responsive polypeptide-polysaccharide depot for concurrent in situ chemotherapy and brachytherapy was developed by encapsulating vincristine into iodine-125 radionuclide labeled hydrogel. This depot hydrogel was prepared by dynamic covalent bonds of Schiff base between aldehydeated hyaluronic acid and polyethylene glycol-polytyrosine. Therefore, this hydrogel enables smart response to tumor acidic microenvironment, rapid release of the encapsulated vincristine and an enhanced uptake effect by tumor cells, which significantly reduces IC50 of vincristine for the anaplasia Wilms' tumor cells in vitro. This depot hydrogel shows excellent stability and biocompatibility, and maintains for 14 days after in situ injection in a postoperative model of anaplasia Wilms' tumor. After injection at the cavity of tumor excision, responsively-released vincristine and the radioactive iodine-125 exerted excellent killing effects on residual tumor cells, inhibiting tumor relapse and liver metastasis of the recurrent tumor. Hence, this study proposes an effective therapeutic strategy for inhibiting anaplasia Wilms' tumor recurrence, which provides a new approach for concurrent postoperative chemo-radiotherapy and a desirable guidance in regimen execution of pediatric refractory tumors.

Submegahertz Nucleation of Plasmonic Vapor Microbubbles near a Solid Vertical Boundary.

Laser triggered and photothermally induced vapor bubbles have emerged as promising approaches to facilitate optomechanical energy conversion for numerous applications in microfluidics and nanofluidics. Here, we report an observation of spontaneously triggered periodic nucleation of plasmonic vapor bubbles near a rigid sidewall with readily tuned nucleation frequency from 0.8 kHz to over 200 kHz. The detailed collapsing process of the vapor bubbles was experimentally and numerically investigated. We find that the lateral migration of residual bubbles toward the sidewall refreshes the laser spot area, terminates the subsequent steady bubble growth, and leads to the repeatable bubble nucleation. A mathematic model regarding the Kelvin impulses was derived. It shows that the competition between the rigid boundary induced Bjerknes force and laser irradiation caused thermal Marangoni force on collapsing bubbles governs the process. The model also leads to a criterion of γζ<0.34 for repeatable bubble nucleation, where γ is the normalized distance and ζ thermal Marangoni coefficient. This study demonstrates nucleation of violent vapor bubbles at extreme high frequencies, providing an approach to remotely realize strong localized flows in microfluidics and nanofluidics.

Wheat Stripe Rust Inoculum from the Southwest Dispersed to the East Huang-Huai-Hai Region through Southern Anhui in China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a continuous threat to global wheat production. In 2021, the epidemic of wheat stripe rust in China affected approximately 4.5 million hectares, resulting in severe yield losses. When confronted with the epidemic, tracing the sources of the pathogen can offer valuable insights for disease prevention and control. This study was conducted to analyze the genetic structure, aerodynamics, geographical features, and cultivation practices of the pathogen population in various wheat-producing regions, and to further reveal the spread patterns of the stripe rust pathogens in China. The findings indicated an overall trend of the pathogen dissemination from the west to the east. The pathogen was primarily spread from the northwestern region to the Huang-Huai-Hai region through the Guanzhong Plain and the NanXiang Plain. Meanwhile, the pathogen was also spread eastward from the southwestern region to the lower reaches of the Yangtze River, utilizing the Jianghan Plain as a bridge and the Yangtze River Valley in southwestern Anhui as the main pathway. Furthermore, the pathogen spread northward into Shandong under the driving force of the southeast winds. The findings of this study may provide valuable insights for the integrated management of wheat stripe rust in China.

High-percentage new energy distribution network line loss frequency division prediction based on wavelet transform and BIGRU-LSTM.

The access of new energy improves the flexibility of distribution network operation, but also leads to more complex mechanism of line loss. Therefore, starting from the nonlinear, fluctuating and multi-scale characteristics of line loss data, and based on the idea of decomposition prediction, this paper proposes a new method of line loss frequency division prediction based on wavelet transform and BIGRU-LSTM (Bidirectional Gated Recurrent Unit-Long Short Term Memory Network).Firstly, the grey relation analysis and the improved NARMA (Nonlinear Autoregressive Moving Average) correlation analysis method are used to extract the non-temporal and temporal influencing factors of line loss, and the corresponding feature data set is constructed. Then, the historical line loss data is decomposed into physical signals of different frequency bands by using wavelet transform, and the multi-dimensional input data of the prediction network is formed with the above characteristic data set. Finally, the BIGRU-LSTM prediction network is built to realize the probabilistic prediction of high-frequency and low-frequency components of line loss. The effectiveness and applicability of the method proposed in this paper were verified through numerical simulation. By dividing the line loss data into different frequency bands for frequency prediction, the mapping relationship between different line loss components and influencing factors was accurately matched, thereby improving the prediction accuracy.

Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent Mitophagy.

Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic - pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.

Bioactive daphnane diterpenes from the flower buds of Daphne genkwa (Thymelaeaceae).

Four diterpenes of the daphnane type were isolated from a methanol extract of the flower buds of Daphne genkwa, the two of them were new structures named genkwadanes J (1) and K (2). Their structures were determined based on analysis of their 1D- and 2D-NMR, HRESIMS and ECD calculations. Among the isolates, the cytotoxicity was assessed via the MTT method using the K562, MCF-7 and HeLa cancer cell lines, the positive control was taxol. Compounds 1 and 3 exhibited appreciable cytotoxic activity against the K562 cancer cell line with IC50 values between 6.58 and 5.33 µM. Compounds 2 and 4 showed noteworthy inhibitory effects against the MCF-7 cell line with IC50 values of 3.25 and 2.56 µM, respectively. All compounds showed weak cytotoxicities to the Hela cell line with IC50 values in the range of 20.19-55.23 µM.

Understanding the Processing Quality Problem for Cutting Ceramic Materials Using the Thermal-Controlled Fracture Method Induced by a Single-Surface Heat Source.

The thermal-controlled fracture method has been increasingly focused upon in the high-quality cutting of advanced ceramic materials due to its excellent characteristics. The successful application of this method in cutting ceramics mainly depends on the volumetric heating effect. However, most ceramics are treated using the surface heating mode. For the surface heating mode, the processing quality, including fracture trajectory and fracture quality, is far lower than the industrial application standards. This work was conducted to reveal the mechanism of this processing quality. Experiments involving cutting ceramics in single-surface heating mode indicate that the fracture trajectories of the upper and lower surfaces display a significant inconsistency, and the fracture quality is worse than that using the dual-surface heating mode. A cutting model was established to calculate the thermal stress distribution and to simulate the crack-propagation behaviors. The simulation results show good agreement with the experiment and provide the stress distribution, and are used to understand the reason for the processing quality problem. The mechanism of the trajectory deviation and uneven distribution of the fracture quality is revealed based on the simulation and calculation results. This study helps provide a deep understanding of the processing problems arising from this method and thus helps to innovate high-quality processing methods in this field.

Scaling variation in the pinch-off of colloid-polymer mixtures.

HYPOTHESIS: The scaling laws of drop pinch-off are known to be affected by drop compositions including dissolved polymers and non-Brownian particles. When the size of the particles is comparable to the characteristic length scale of the polymer network, these particles may interact strongly with the polymer environment, leading to new types of scaling behaviors not reported before. EXPERIMENTS: Using high-speed imaging, we experimentally studied the time evolution of the neck diameter hmin of drops composed of silica nanoparticles dispersed in PEO solution when extruded from a nozzle. FINDINGS: After initial Newtonian necking with hmin âˆ¼ t2/3, the subsequent stage may exhibit scaling variation, characterized by either exponential or power-law decay, depending on the nanoparticle volume fraction ϕ. The exponential decay hmin âˆ¼ e-t/τ signifies the coil-stretch transition in typical viscoelastic suspensions. We conducted an analysis of the power-law scenario hmin âˆ¼ tα at high ϕ, categorizing the entire process into three distinct regimes based on the exponents α. The dependences of critical thicknesses at transition points and exponents on polymer concentration offer initial insights into the potential transition from heterogeneous to homogeneous thinning in the mixture. This novel scaling variation bears implications for accurately predicting and controlling droplet fragmentation in industrial applications.

Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN 177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN 177STYR (H3N4) of IgG4, EEQYN 227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.

Transcriptomic Hallmarks of Hypoxic-Ischemic Brain Injury: Insights from an in Vitro Model.

BACKGROUND: Hypoxic-ischemic injury of neurons is a pathological process observed in several neurological conditions, including ischemic stroke and neonatal hypoxic-ischemic brain injury (HIBI). An optimal treatment strategy for these conditions remains elusive. The present study delved deeper into the molecular alterations occurring during the injury process in order to identify potential therapeutic targets. METHODS: Oxygen-glucose deprivation/reperfusion (OGD/R) serves as an established in vitro model for the simulation of HIBI. This study utilized RNA sequencing to analyze rat primary hippocampal neurons that were subjected to either 0.5 or 2 h of OGD, followed by 0, 9, or 18 h of reperfusion. Differential expression analysis was conducted to identify genes dysregulated during OGD/R. Time-series analysis was used to identify genes exhibiting similar expression patterns over time. Additionally, functional enrichment analysis was conducted to explore their biological functions, and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for validation of hub-gene expression. RESULTS: The study included a total of 24 samples. Analysis revealed distinct transcriptomic alterations after OGD/R processes, with significant dysregulation of genes such as Txnip, Btg2, Egr1 and Egr2. In the OGD process, 76 genes, in two identified clusters, showed a consistent increase in expression; functional analysis showed involvement of inflammatory responses and signaling pathways like tumor necrosis factor (TNF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interleukin 17 (IL-17). PPI network analysis suggested that Ccl2, Jun, Cxcl1, Ptprc, and Atf3 were potential hub genes. In the reperfusion process, 274 genes, in three clusters, showed initial upregulation followed by downregulation; functional analysis suggested association with apoptotic processes and neuronal death regulation. PPI network analysis identified Esr1, Igf-1, Edn1, Hmox1, Serpine1, and Spp1 as key hub genes. qRT-PCR validated these trends. CONCLUSIONS: The present study provides a comprehensive transcriptomic profile of an in vitro OGD/R process. Key hub genes and pathways were identified, offering potential targets for neuroprotection after hypoxic ischemia.

Self-enhanced localized alkalinity at the encapsulated Cu catalyst for superb electrocatalytic nitrate/nitrite reduction to NH3 in neutral electrolyte.

The electrocatalytic nitrate/nitrite reduction reaction (eNOx-RR) to ammonia (NH3) is thermodynamically more favorable than the eye-catching nitrogen (N2) electroreduction. To date, the high eNOx-RR-to-NH3 activity is limited to strong alkaline electrolytes but cannot be achieved in economic and sustainable neutral/near-neutral electrolytes. Here, we construct a copper (Cu) catalyst encapsulated inside the hydrophilic hierarchical nitrogen-doped carbon nanocages (Cu@hNCNC). During eNOx-RR, the hNCNC shell hinders the diffusion of generated OH- ions outward, thus creating a self-enhanced local high pH environment around the inside Cu nanoparticles. Consequently, the Cu@hNCNC catalyst exhibits an excellent eNOx-RR-to-NH3 activity in the neutral electrolyte, equivalent to the Cu catalyst immobilized on the outer surface of hNCNC (Cu/hNCNC) in strong alkaline electrolyte, with much better stability for the former. The optimal NH3 yield rate reaches 4.0 moles per hour per gram with a high Faradaic efficiency of 99.7%. The strong-alkalinity-free advantage facilitates the practicability of Cu@hNCNC catalyst as demonstrated in a coupled plasma-driven N2 oxidization with eNOx-RR-to-NH3.