Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease.

With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.

PCAS: An Integrated Tool for Multi-Dimensional Cancer Research Utilizing Clinical Proteomic Tumor Analysis Consortium Data.

Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research.

2.1 µm multi-quantum well laser epitaxially grown on on-axis (001) InP/SiO2/Si substrate fabricated by ion-slicing.

A cost-effective method to achieve a 2-3 µm wavelength light source on silicon represents a major challenge. In this study, we have developed a novel approach that combines an epitaxial growth and the ion-slicing technique. A 2.1 µm wavelength laser on a wafer-scale heterogeneous integrated InP/SiO2/Si (InPOI) substrate fabricated by ion-slicing technique was achieved by epitaxial growth. The performance of the lasers on the InPOI are comparable with the InP, where the threshold current density (Jth) was 1.3 kA/cm2 at 283 K when operated under continuous wave (CW) mode. The high thermal conductivity of Si resulted in improved high-temperature laser performance on the InPOI. The proposed method offers a novel means of integrating an on-chip light source.

Socioeconomic and sociodemographic correlations to COVID-19 variability in the United States in 2020.

The COVID-19 pandemic provided an additional spotlight on the longstanding socioeconomic/health impacts of redlining and has added to the myriad of environmental justice issues, which has caused significant loss of life, health, and productive work. The Centers for Disease Control and Prevention (CDC) reports that a person with any selected underlying health conditions is more likely to experience severe COVID-19 symptoms, with more than 81% of COVID-19-related deaths among people aged 65 years and older. The effects of COVID-19 are not homogeneous across populations, varying by socioeconomic status, PM2.5 exposure, and geographic location. This variability is supported by analysis of existing data as a function of the number of cases and deaths per capita/1,00,000 persons. We investigate the degree of correlation between these parameters, excluding health conditions and age. We found that socioeconomic variables alone contribute to ~40% of COVID-19 variability, while socioeconomic parameters, combined with political affiliation, geographic location, and PM2.5 exposure levels, can explain ~60% of COVID-19 variability per capita when using an OLS regression model; socioeconomic factors contribute ~28% to COVID-19-related deaths. Using spatial coordinates in a Random Forest (RF) regressor model significantly improves prediction accuracy by ~120%. Data visualization products reinforce the fact that the number of COVID-19 deaths represents 1% of COVID-19 cases in the US and globally. A larger number of democratic voters, larger per-capita income, and age >65 years is negatively correlated (associated with a decrease) with the number of COVID cases per capita. Several distinct regions of negative and positive correlations are apparent, which are dominated by two major regions of anticorrelation: (1) the West Coast, which exhibits high PM2.5 concentrations and fewer COVID-19 cases; and (2) the middle portion of the US, showing mostly high number of COVID-19 cases and low PM2.5 concentrations. This paper underscores the importance of exercising caution and prudence when making definitive causal statements about the contribution of air quality constituents (such as PM2.5) and socioeconomic factors to COVID-19 mortality rates. It also highlights the importance of implementing better health/lifestyle practices and examines the impact of COVID-19 on vulnerable populations, particularly regarding preexisting health conditions and age. Although PM2.5 contributes comparable deaths (~7M) per year, globally as smoking cigarettes (~8.5M), quantifying any causal contribution toward COVID-19 is non-trivial, given the primary causes of COVID-19 death and confounding factors. This becomes more complicated as air pollution was reduced significantly during the lockdowns, especially during 2020. This statistical analysis provides a modular framework, that can be further expanded with the context of multilevel analysis (MLA). This study highlights the need to address socioeconomic and environmental disparities to better prepare for future pandemics. By understanding how factors such as socioeconomic status, political affiliation, geographic location, and PM2.5 exposure contribute to the variability in COVID-19 outcomes, policymakers and public health officials can develop targeted strategies to protect vulnerable populations. Implementing improved health and lifestyle practices and mitigating environmental hazards will be essential in reducing the impact of future public health crises on marginalized communities. These insights can guide the development of more resilient and equitable health systems capable of responding effectively to similar future scenarios.

Deciphering unique and shared interactions between the human gut microbiota and oral antidiabetic drugs.

The administration of oral antidiabetic drugs (OADs) to patients with type 2 diabetes elicits distinct and shared changes in the gut microbiota, with acarbose and berberine exhibiting greater impacts on the gut microbiota than metformin, vildagliptin, and glipizide. The baseline gut microbiota strongly associates with treatment responses of OADs.

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor.

The type-1 cannabinoid receptor (CB1R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB1R ligands. In this study, CB1R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB1R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB1R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB1R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB1R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB1R, which can be used to control psychiatric disorders and drug abuse.

Multi-omics unveils tryptophan metabolic pathway as a key pathway influencing residual feed intake in Duroc swine.

The genetic trait of residual feed intake (RFI) holds considerable importance in the swine industry. Recent research indicates that the gut microbiota of pigs plays a pivotal role in the manifestation of the RFI trait. Nevertheless, the metabolic pathways involved in the functioning of these microorganisms remain elusive. Thus, based on the ranking of the RFI trait in Duroc pigs, the present study selected the top 10 and bottom 10 pigs as the experimental subjects. The distribution and metabolite differences of cecal microbiota were analyzed using 16S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. The low RFI cecal group was named LRC, and the high RFI cecal group was named HRC. The results indicate that the LRC group had lower RFI, feed conversion ratio (FCR), average daily feed intake (ADFI) (p < 0.001), and thinner backfat (p < 0.05) compared with the HRC group. We simultaneously recorded the foraging behavior as well, the LRC group had a significant increase in total time spent at the feeder per day (TPD) (p < 0.05) and a significant increase in average feed intake per mins (AFI) and the number of visits to the feeder per day (NVD) compared to the HRC group (p < 0.001). Clostridium_XVIII, Bulleidia, and Intestinimonas were significantly enriched in the LRC group (p < 0.01), while Sutterella, Fusobacterium, and Bacteroides were significantly increased in the HRC group (p < 0.01). In the metabolome, we detected 390 (248 metabolites up and 142 down in the LRC compared with HRC), and 200 (97 metabolites up and 103 down in the LRC compared with HRC) differential metabolites in positive and negative ionization modes. The comprehensive analysis found that in the LRC group, Escherichia and Eubacterium in the gut may increase serotonin content, respectively. Bacteroides may deplete serotonin. We suggest that the RFI may be partly achieved through tryptophan metabolism in gut microbes. In individuals with low RFI, gut microbes may enhance feed efficiency by enhancing host synthesis and metabolism of tryptophan-related metabolites.

Incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated haemophilia A.

INTRODUCTION: Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by lack or deficiency of coagulation factor VIII. AIM: The aim of this study is to determine the incidence and treatment-related risk factors of inhibitor development after intensive FVIII replacement for major orthopaedic surgery in previous treated persons with HA. METHODS: A total of 151 HA who underwent 221 major orthopaedic surgical procedures after intensive FVIII treatment were reviewed. The results of inhibitor tests were collected. Potential clinical risk factors for inhibitor development were analyzed. RESULTS: 111 people were diagnosed with severe HA. Thirty-seven persons (24.5%) had history of previous intensive FVIII treatment for surgical procedure. They received a mean perioperative cumulative FVIII of 498 iu/kg within first week after surgery. Seven cases (4.6%) developed an inhibitor post-operatively in our study. Surgical procedure for pseudotumor and the group of persons who experienced postoperative complications had the higher incidence of inhibitor development (9.5%, 13.3% respectively). Only previous history for intensive FVIII exposure was considered as a significant predictor for postoperative inhibitor development after multivariate logistic regression analysis (OR: 29.5, P = 0.002). CONCLUSION: The incidence of inhibitor development in previously treated persons with HA undergoing major orthopaedic surgery was 4.6% and the history of previous intensive FVIII treatment for surgery was associated with higher risk of inhibitor development.

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.

Efficacy and Functional Mechanisms of a Two-Stage Pretreatment Approach Based on Alkali and Ionic Liquid for Bioconversion of Waste Medium-Density Fiberboard.

A novel pretreatment strategy utilizing a combination of NaOH and 1-Butyl-3-methylimidazolium chloride ([Bmim]Cl) was proposed to enhance the enzymatic hydrolysis of abandoned Medium-density fiberboard (MDF). The synergistic effect of NaOH and [Bmim]Cl pretreatment significantly improved the glucose yield, reaching 445.8 mg/g within 72 h, which was 5.04 times higher than that of the untreated samples. The working mechanism was elucidated according to chemical composition, as well as FTIR, 13C NMR, XRD, and SEM analyses. The combined effects of NaOH and [Bmim]Cl led to lignin degradation, hemicellulose removal, the destruction and erosion of crystalline regions, pores, and an irregular microscopic morphology. In addition, by comparing the enzymatic hydrolysis sugar yield and elemental nitrogen content of untreated MDF samples, eucalyptus, and hot mill fibers (HMF), it was demonstrated that the presence of adhesives and additives in waste MDF significantly influences its hydrolysis process. The sugar yield of untreated MDF samples (88.5 mg/g) was compared with those subjected to hydrothermal pretreatment (183.2 mg/g), Ionic liquid (IL) pretreatment (406.1 mg/g), and microwave-assisted ionic liquid pretreatment (MWI) (281.3 mg/g). A long water bath pretreatment can reduce the effect of adhesives and additives on the enzymatic hydrolysis of waste MDF. The sugar yield produced by the combined pretreatment proposed in this study and the removal ability of adhesives and additives highlight the great potential of our pretreatment technology in the recycling of waste fiberboard.

Controlling release of astaxanthin in ß-sitosterol oleogel-based emulsions via different self-assembled mechanisms and composition of the oleogelators.

In this study, three types of ß-sitosterol-based oleogels (ß-sitosterol + Î³-oryzanol oleogels, ß-sitosterol + lecithin, oleogels and ß-sitosterol + monostearate oleogels), loaded with astaxanthin, were employed as the oil phase to create oleogel-based emulsions (SO, SL, and SM) using high-pressure homogenization. The microstructure revealed that fine-scale crystals were dispersed within the oil phase of the droplets in the ß-sitosterol oleogel-based emulsion. The bioaccessibility of astaxanthin was found to be 58.13 %, 51.24 %, 36.57 %, and 45.72 % for SM, SL, SO, and the control group, respectively. Interestingly, the release of fatty acids was positively correlated with the availability of astaxanthin (P = 0.981). Further analysis of FFAs release and kinetics indicated that the structural strength of the oil-phase in the emulsions influenced the degree and rate of lipolysis. Additionally, the micellar fraction analysis suggested that the nature and composition of the oleogelators in SM and SL also impacted lipolysis and the bioaccessibility of astaxanthin. Furthermore, interfacial binding of lipase and isothermal titration calorimetry (ITC) measurements revealed that the oleogel network within the oil phase of the emulsion acted as a physical barrier, hindering the interaction between lipase and lipid. Overall, ß-sitosterol oleogel-based emulsions offer a versatile platform for delivering hydrophobic molecules, enhancing the bioavailability of active compounds, and achieving sustained release.

Theoretical exploration of the phenolic compounds' inhibition mechanism of heterocyclic aromatic amines in roasted beef patties by density functional theory.

The ability of spices (bay leaf, star anise, and red pepper) and their characteristic phenolic compounds (quercetin, kaempferol, and capsaicin) to inhibit Heterocyclic aromatic amines (HAAs) in roasted beef patties were compared. Density functional theory (DFT) was used to reveal phenolic compounds interacting with HAAs-related intermediates and free radicals to explore possible inhibitory mechanisms for HAAs. 3 % red chili and 0.03 % capsaicin reduced the total HAAs content by 57.09 % and 68.79 %, respectively. DFT demonstrated that this was due to the stronger interaction between capsaicin and the ß-carboline HAAs intermediate (Ebind = -32.95 kcal/mol). The interaction between quercetin and phenylacetaldehyde was found to be the strongest (Ebind = -17.47 kcal/mol). Additionally, DFT indicated that capsaicin reduced the carbonyl content by transferring hydrogen atoms (HAT) to eliminate HO·, HOO·, and carbon-centered alkyl radicals. This study provided a reference for the development of DFT in the control of HAAs.

Low-Temperature Cross-Linked Hole Transport Layer for High-Performance Blue Quantum-Dot Light-Emitting Diodes.

Quantum-dot light-emitting diodes (QLEDs), a kind of promising optoelectronic device, demonstrate potential superiority in next-generation display technology. Thermal cross-linked hole transport materials (HTMs) have been employed in solution-processed QLEDs due to their excellent thermal stability and solvent resistance, whereas the unbalanced charge injection and high cross-linking temperature of cross-linked HTMs can inhibit the efficiency of QLEDs and limit their application. Herein, a low-temperature cross-linked HTM of 4,4'-bis(3-(((4-vinylbenzyl)oxy)methyl)-9H-carbazol-9-yl)-1,1'-biphenyl (DV-CBP) with a flexible styrene side chain is introduced, which reduces the cross-linking temperature to 150 °C and enhances the hole mobility up to 1.01 × 10-3 cm2 V-1 s-1. More importantly, the maximum external quantum efficiency of 21.35% is successfully obtained on the basis of the DV-CBP as a cross-linked hole transport layer (HTL) for blue QLEDs. The low-temperature cross-linked high-mobility HTL using flexible side chains could be an excellent alternative for future HTL development.

A critical event frequent lead to reversible spinal cord injury during vertebral column resection surgery.

OBJECTIVE: To report a "critical phase" (between osteotomy completion and correction beginning) that will frequently lead to the reversible intraoperative neurophysiological monitoring (IOM) change during posterior vertebral column resection (PVCR) surgery. METHODS: The study sample consisted of 120 patients with severe spine deformity who underwent PVCR and deformity correction surgeries. Those patients were recruited consecutively from 2010 to 2018 January in our spine center. The detailed IOM data (the amplitude of MEP & SEP) and its corresponding surgical points were collected prospectively. Early and long-term postoperative neurologic outcomes were assessed for the following functions: motor, sensory, and pain at immediate postoperative and 1-year post-operation in this cases series. RESULTS: A total of 105 (105/120) patients presented varying degrees of IOM reduction in the critical phase; the mean IOM amplitude retention vs rescue rate was 27% ± 11.2 versus 58% ± 16.9, P < 0.01 (MEP) & 34% ± 8.3 versus 66% ± 12.4 P < 0.01 (SEP). Patients with postoperative spinal deficits often had a significantly longer IOM-alerting duration than the patients without (p < 0.01, Mann-Whitney U-test), and IOM-alerting duration greater than 39.5 min was identified as an independent predictor of the risk of postoperative spinal deficits. CONCLUSIONS: The reversible IOM events probably often appear in the critical phase during PVCR surgery. The new postoperative spinal deficits are possible for patients without satisfied IOM recovery or alerting duration greater than 39.5 min. Timely and suitable surgical interventions are useful for rescuing the IOM alerts.

Triglyceride-glucose index and mortality risk in individuals with or without chronic kidney disease: Insights from a national survey of United States adults, 1999-2018.

BACKGROUND AND AIMS: The Triglyceride-Glucose Index (TyG) has been proposed as a predictor to mortality, yet its association remains incompletely understood for individuals with or without chronic kidney disease (CKD). METHODS AND RESULTS: We analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018. CKD was defined as eGFR level <60 ml/min/1.73 m2 or urinary albumin creatinine ratio ≥30 mg/g. We employed the Cox proportional-hazards model to evaluate the incident risk of mortality associated with TyG among both non-CKD and CKD individuals. In the current analysis, 19,426 individuals were without CKD, while 2975 individuals had CKD. The overall mean TyG was 8.65, with significant difference between non-CKD and CKD individuals (8.60 vs 8.95, P < 0.001). The TyG index exhibited linear associations with incident cardiovascular disease (CVD) mortality and all-cause mortality among non-CKD and CKD individuals, respectively. A per-unit increase in the TyG index was significantly associated with CVD mortality for both non-CKD (HR = 1.24, 95%CI = 1.09-1.41) and CKD participants (HR = 1.19, 95%CI = 1.04-1.36), with no significant difference in the associations between the two groups (P = 0.091). For both non-CKD and CKD participants, TyG index was significantly associated with CVD mortality and all-cause mortality among those with age <65, but not for those with age ≥65. CONCLUSIONS: Our findings underscore the TyG index's as a valuable predictive tool for assessing the risk of all-cause and CVD mortality in both individuals with and without CKD.

A silicon photoanode protected with TiO2/stainless steel bilayer stack for solar seawater splitting.

Photoelectrochemical seawater splitting is a promising route for direct utilization of solar energy and abundant seawater resources for H2 production. However, the complex salinity composition in seawater results in intractable challenges for photoelectrodes. This paper describes the fabrication of a bilayer stack consisting of stainless steel and TiO2 as a cocatalyst and protective layer for Si photoanode. The chromium-incorporated NiFe (oxy)hydroxide converted from stainless steel film serves as a protective cocatalyst for efficient oxygen evolution and retarding the adsorption of corrosive ions from seawater, while the TiO2 is capable of avoiding the plasma damage of the surface layer of Si photoanode during the sputtering of stainless steel catalysts. By implementing this approach, the TiO2 layer effectively shields the vulnerable semiconductor photoelectrode from the harsh plasma sputtering conditions in stainless steel coating, preventing surface damages. Finally, the Si photoanode with the bilayer stack inhibits the adsorption of chloride and realizes 167 h stability in chloride-containing alkaline electrolytes. Furthermore, this photoanode also demonstrates stable performance under alkaline natural seawater for over 50 h with an applied bias photon-to-current efficiency of 2.62%.

Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.

Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.

Chromosome-level Alstonia scholaris genome unveils evolutionary insights into biosynthesis of monoterpenoid indole alkaloids.

Alstonia scholaris of the Apocynaceae family is a medicinal plant with a rich source of bioactive monoterpenoid indole alkaloids (MIAs), which possess anti-cancer activity like vinca alkaloids. To gain genomic insights into MIA biosynthesis, we assembled a high-quality chromosome-level genome for A. scholaris using nanopore and Hi-C data. The 444.95 Mb genome contained 35,488 protein-coding genes. A total of 20 chromosomes were assembled with a scaffold N50 of 21.75 Mb. The genome contained a cluster of strictosidine synthases and tryptophan decarboxylases with synteny to other species and a saccharide-terpene cluster involved in the monoterpenoid biosynthesis pathway of the MIA upstream pathway. The multi-omics data of A. scholaris provide a valuable resource for understanding the evolutionary origins of MIAs and for discovering biosynthetic pathways and synthetic biology efforts for producing pharmaceutically useful alkaloids.

Photothermal Synergic Cross-Linking Hole Transport Layer for Highly Efficient RGB QLEDs.

Developing an insoluble cross-linkable hole transport layer (HTL) plays an important role for solution-processed quantum dots light-emitting diodes (QLEDs) to fabricate a multilayer device with separated quantum dots layers and HTLs. In this work, a facile photothermal synergic cross-linking strategy is simultaneous annealing and UV irradiation to form the high-quality cross-linked film as the HTL without any photoinitiator, which efficiently reduces the cross-linking temperature to the low temperature of 130 °C and enhances the hole mobility of the 3-vinyl-9-{4-[4-(3-vinylcarbazol-9-yl)phenyl]phenyl}carbazole (CBP-V) thin films. The obtained high-quality cross-linked CBP-V films exhibited smooth morphology, excellent solvent resistance, and high mobility. Moreover, the high-performance red, green, and blue (RGB) QLEDs are successfully fabricated by using the photothermal synergic cross-linked HTLs, which achieved the maximum external quantum efficiency of 25.69, 24.42, and 16.51%, respectively. This work presents a strategy of using the photothermal synergic cross-linked HTLs for fabrication of high-performance QLEDs and advancing their related device applications.