Comment on Dheyab AM. et al.'s "Long-Term Efficacy of Oral Valganciclovir in Presumed Cytomegalovirus Unilateral Hypertensive Anterior Uveitis".

The inclusion criteria of patients in this study were inconsistent especially in distinguishing Fuchs' uveitis and herpetic uveitis from Posner-Schlossman syndrome, indicating well-defined inclusion criteria were needed. CMV anterior uveitis and Posner-Schlossman syndrome may not be the same disease, CMV may only act as a triggering factor for Posner-Schlossman syndrome, and the clinical manifestations of mild anterior segment inflammation were mainly caused by inflammatory reactions mediated by autoimmune factors. Although the antiviral medication was important in the treatment of Posner-Schlossman syndrome, the role of other treatment methods especially topical steroids should not be ignored.

The beginning of iron corrosion - high-resolution visualization with 3D electron tomography.

Understanding the genesis and early-phase reactions of iron corrosion is essential for the early detection, mitigation and prevention of metal degradation. In this work, high-resolution 3D tomography of metallic iron oxidation was acquired using high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In particular, dendritic capillaries (<0.5 nm) were observed during the initial oxidation of fresh nanoscale zero-valent iron due to the differential oxygen diffusion and iron atoms migration. This observation led to the proposal of a nanoscale "pothole" model for early-phase corrosion, wherein hollowing out of the metal nanoparticle and formation of nanovoids beneath the iron/oxide interface through Kirkendall effect. Coalescence of the nanocapillaries results in the ultimate collapse of metal structure and/or functional failure. Using nanoscale zero-valent iron as a research model, this work provides unprecedented insights into the nano- and atomic-scale mechanisms of iron oxidation, paving the way for advanced detection and prevention strategies for iron corrosion.

Efficacy and safety of intranasal insulin on postoperative cognitive dysfunction in elderly patients after laparoscopic radical resection of colorectal cancer: a double-blind pilot study.

Objective: To evaluate the efficacy and safety of intranasal insulin on postoperative cognitive dysfunction (POCD) in elderly patients after laparoscopic radical resection of colorectal cancer. Methods: Older patients scheduled for laparoscopic radical resection of colorectal cancer at Beijing Luhe Hospital, Capital Medical University, between August 2023 and November 2023, were enrolled in this double-blind pilot study. Patients were randomized to the control and insulin groups at a 1:1 ratio. The primary outcome was the rate of POCD at postoperative 7 days. Results: A total of 61 patients (30 in the insulin group) were analyzed. The insulin group had a significantly lower POCD rate compared with the control group at postoperative day 7 [4(13.3%) vs. 12 (38.7%), p = 0.024]. The serum levels of IL-6, TNF-α and S100ß at T2-5 in the insulin group were significantly lower than those of the control group (IL-6: mean difference at T2, -4.14, p = 0.036; T3, -3.84, p = 0.039; T4, -3.37, p = 0.013; T5, -2.57, p = 0.042; TNF-α: mean difference at T2, -3.19, p = 0.002; T3, -2.35, p = 0.028; T4, -2.30, p = 0.019; T5, -1.96, p = 0.0181; S100ß: mean difference at T2, -8.30, p = 0.019; T3, -23.95, p = 0.020; T4, -20.01, p = 0.023; T5, -17.67, p = 0.010). No insulin allergic reactions, nasal irritation, or hypoglycemic reactions were observed in either of the groups. Conclusion: Intranasal insulin may decrease the risk of POCD and inhibit the elevated serum IL-6, TNF-α, and S100ß levels in elderly patients after laparoscopic radical resection of colorectal cancer, which proves that intranasal insulin may be a promising therapeutic option for POCD. Clinical trial registration: Identifier, ChiCTR2300074423.

A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection.

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

Oxygen vacancy-promoted photocatalytic H2O2 production over bismuth oxybromide nanosheets.

Hydrogen peroxide (H2O2) is an essential and versatile oxidant. The photocatalytic production of H2O2 is a promising alternative to the conventional anthraquinone oxidation process. In this work, BiOBr nanosheets with oxygen vacancies (OVs) were successfully synthesized by a solvothermal method in the presence of mannitol. The character of the nanosheets shortened the diffuse length of charge carriers, which is beneficial for the charge separation. The introduction of OVs enhanced the visible light absorption and also improved the carrier separation. Furthermore, OVs enhanced the activation of O2 molecules and facilitated the generation of ˙O2-. As a result, the products exhibited good performance in photocatalytic H2O2 production. After introducing HCOOH, the yield of H2O2 was further enhanced by a factor of 50, from 3 µmol h-1 to 150 µmol h-1. This work provides a reference to design high performance photocatalysts for H2O2 production through defect engineering.

Carbon Dioxide Anion Radicals Assisted Highly Efficient Photocatalytic H2O2 Production over Bi(C2O4)OH.

Carbon dioxide anion radical (CO2•-) can act as a versatile single electron reductant, but its generation pathways are quite limited. Herein, we demonstrate that oxalic acid (OA) could be effectively and continuously utilized to produce CO2•- over Bi(C2O4)OH, a novel photocatalyst, under light irradiation. Bi(C2O4)OH would proceed with self-redox reactions under the light irradiation producing CO2•-, through the oxidation of C2O42-. OA in the solution could recoordinate with Bi3+, thus maintaining the structure of the photocatalysts and the stability of the reactions. Benefiting from the fast reaction between CO2•- and O2 in forming •O2-, hydrogen peroxide (H2O2) would be efficiently produced (219.0 µmol/h). This study proposes a novel approach for harnessing OA containing wastewater and explores its potential application in the efficient production of H2O2.

CO2 -Mediated Photocatalytic Chlorine Production Over Bismuth Oxychloride in Chloride Solution.

As one of the most commonly bulky chemicals, chlorine is conventionally manufactured by electrolysis of NaCl solution in the chlor-alkali process, which requires a huge supply of electrical energy. The photocatalytic route to produce chlorine by using solar energy and NaCl solution offers a promising strategy to reduce energy consumption and bring economic benefits. Herein, it was found that the introduction of CO2 would enhance the productivity of Cl2 from 8.24 µmol⋅h-1 to 39.6 µmol⋅h-1 in NaCl solution over BiOCl. Experimental studies reveal that the CO2 species (CO3 2- ) entered into the crystal texture of BiOCl and the interlayer space between [Bi2 O2 ]2+ slabs were increased and distorted, accelerating the cycle of Cl species. Besides, the cycle of carbonate species also existed and accelerated the reaction efficiency of Cl- oxidation to Cl2 . This work provides a new feasible method of using abundant CO2 resources to accelerate the process of chlorine production via photocatalysis.

Plants' Response to Abiotic Stress: Mechanisms and Strategies.

Abiotic stress is the adverse effect of any abiotic factor on a plant in a given environment, impacting plants' growth and development. These stress factors, such as drought, salinity, and extreme temperatures, are often interrelated or in conjunction with each other. Plants have evolved mechanisms to sense these environmental challenges and make adjustments to their growth in order to survive and reproduce. In this review, we summarized recent studies on plant stress sensing and its regulatory mechanism, emphasizing signal transduction and regulation at multiple levels. Then we presented several strategies to improve plant growth under stress based on current progress. Finally, we discussed the implications of research on plant response to abiotic stresses for high-yielding crops and agricultural sustainability. Studying stress signaling and regulation is critical to understand abiotic stress responses in plants to generate stress-resistant crops and improve agricultural sustainability.

Efficient One-Pot Synthesis of 2,5-Furandicarboxylic Acid from Sugars over Polyoxometalate/Metal-Organic Framework Catalysts.

Converting extensive sugars into value-added 2,5-furandicarboxylic acid (FDCA) has been considered to be a promising approach to developing sustainable substitutes for chemicals from fossil resources. The complicated conversion processes involved multiple cascade reactions and intermediates, which made the design of efficient multifunction catalysts challenging. Herein, we developed a catalyst by introducing phosphotungstic acid (PW) and Co sites into the UiO-66, which achieved a one-pot cascade conversion of fructose-to-FDCA with high conversion (>99 %) and yield (94.6 %) based on the controllable Lewis/Brønsted acid sites and redox sites. Controlled experiments and detailed characterizations show that the multifunctional PW/UiO(Zr, Co) catalysts successfully affords the direct synthesis of FDCA from fructose via dehydration and selective oxidation in the one-pot reaction. Additionally, the MOF catalysts could also efficiently convert various sugars into FDCA, which has broad application prospects. This study provides new strategies for designing multifunctional catalysts to achieve efficient production of FDCA from biomass in the one-pot reaction.

Synthesis, Hole Doping, and Electrical Properties of a Semiconducting Azatriangulene-Based Covalent Organic Framework.

Two-dimensional covalent organic frameworks (2D COFs) containing heterotriangulenes have been theoretically identified as semiconductors with tunable, Dirac-cone-like band structures, which are expected to afford high charge-carrier mobilities ideal for next-generation flexible electronics. However, few bulk syntheses of these materials have been reported, and existing synthetic methods provide limited control of network purity and morphology. Here, we report transimination reactions between benzophenone-imine-protected azatriangulenes (OTPA) and benzodithiophene dialdehydes (BDT), which afforded a new semiconducting COF network, OTPA-BDT. The COFs were prepared as both polycrystalline powders and thin films with controlled crystallite orientation. The azatriangulene nodes are readily oxidized to stable radical cations upon exposure to an appropriate p-type dopant, tris(4-bromophenyl)ammoniumyl hexachloroantimonate, after which the network's crystallinity and orientation are maintained. Oriented, hole-doped OTPA-BDT COF films exhibit electrical conductivities of up to 1.2 × 10-1 S cm-1, which are among the highest reported for imine-linked 2D COFs to date.

Chemical Synthesis of a Keto Sugar Nucleotide.

Keto sugar nucleotides (KSNs) are common and versatile precursors to various deoxy sugar nucleotides, which are substrates for the corresponding glycosyltransferases involved in the biosynthesis of glycoproteins, glycolipids, and natural products. However, there has been no KSN synthesized chemically due to the inherent instability. Herein, the first chemical synthesis of the archetypal KSN TDP-4-keto-6-deoxy-d-glucose (1) is achieved by an efficient and optimized route, providing feasible access to other KSNs and analogues, thereby opening a new avenue for new applications.

High-resolution genome mapping and functional dissection of chlorogenic acid production in Lonicera maackii.

Amur honeysuckle (Lonicera maackii) is a widely used medicinal plant of the Caprifoliaceae family that produces chlorogenic acid. Research on this plant mainly focuses on its ornamental value and medicinal compounds, but a reference genome sequence and molecular resources for accelerated breeding are currently lacking. Herein, nanopore sequencing and high-throughput chromosome conformation capture (Hi-C) allowed a chromosome-level genome assembly of L. maackii (2n = 18). A global view of the gene regulatory network involved in the biosynthesis of chlorogenic acid and the dynamics of fruit coloration in L. maackii was established through metabolite profiling and transcriptome analyses. Moreover, we identified the genes encoding hydroxycinnamoyl-CoA quinate transferase (LmHQT) and hydroxycinnamoyl-CoA shikimic/quinate transferase (LmHCT), which localized to the cytosol and nucleus. Heterologous overexpression of these genes in Nicotiana benthamiana leaves resulted in elevated chlorogenic acid contents. Importantly, HPLC analyses revealed that LmHCT and LmHQTs recombinant proteins modulate the accumulation of chlorogenic acid (CGA) using quinic acid and caffeoyl CoA as substrates, highlighting the importance of LmHQT and LmHCT in CGA biosynthesis. These results confirmed that LmHQTs and LmHCT catalyze the biosynthesis of CGA in vitro. The genomic data presented in this study will offer a valuable resource for the elucidation of CGA biosynthesis and facilitating selective molecular breeding.

A puzzling insensitivity of magnon spin diffusion to the presence of 180-degree domain walls.

We present room-temperature measurements of magnon spin diffusion in epitaxial ferrimagnetic insulator MgAl0.5Fe1.5O4 (MAFO) thin films near zero applied magnetic field where the sample forms a multi-domain state. Due to a weak uniaxial magnetic anisotropy, the domains are separated primarily by 180° domain walls. We find, surprisingly, that the presence of the domain walls has very little effect on the spin diffusion - nonlocal spin transport signals in the multi-domain state retain at least 95% of the maximum signal strength measured for the spatially-uniform magnetic state, over distances at least five times the typical domain size. This result is in conflict with simple models of interactions between magnons and static domain walls, which predict that the spin polarization carried by the magnons reverses upon passage through a 180° domain wall.

Predictors of relapse in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is a large-vessel vasculitis with high relapse rate. Longitudinal studies identifying risk factors of relapse are limited. We aimed to analyze the associated factors and develop a risk prediction model for relapse. METHODS: We analyzed the associated factors for relapse in a prospective cohort of 549 TAK patients from the Chinese Registry of Systemic Vasculitis cohort between June 2014 and December 2021 using univariate and multivariate Cox regression analyses. We also developed a prediction model for relapse, and stratified patients into low-, medium-, and high-risk groups. Discrimination and calibration were measured using C-index and calibration plots. RESULTS: At a median follow-up of 44 (IQR 26-62) months, 276 (50.3%) patients experienced relapses. History of relapse (HR 2.78 [2.14-3.60]), disease duration <24 months (HR 1.78 [1.37-2.32]), history of cerebrovascular events (HR 1.55 [1.12-2.16]), aneurysm (HR 1.49 [1.10-2.04], ascending aorta or aortic arch involvement (HR 1.37 [1.05-1.79]), elevated high-sensitivity C-reactive protein level (HR 1.34 [1.03-1.73]), elevated white blood cell count (HR 1.32 [1.03-1.69]), and the number of involved arteries ≥6 (HR 1.31 [1.00-1.72]) at baseline independently increased the risk of relapse and were included in the prediction model. The C-index of the prediction model was 0.70 (95% CI 0.67-0.74). Predictions correlated with observed outcomes on the calibration plots. Compared to the low-risk group, both medium and high-risk groups had a significantly higher relapse risk. CONCLUSIONS: Disease relapse is common in TAK patients. This prediction model may help to identify high-risk patients for relapse and assist clinical decision-making.

How does the internal distribution of microplastics in Scylla serrata link with the antioxidant response in functional tissues?

Crabs can live in diverse lifestyles in both water and benthic environments, which are the basin of microplastics (MPs) inputs. Edible crabs with large consuming quantity, e.g., Scylla serrata were subjected to accumulate MPs in their tissues from surrounding environments and generate biological damages. However, no related research has been conducted. In order to accurately assess the potential risks to both crabs and humans consuming MPs contaminated crabs, S. serrata were exposed to different concentrations (2, 200 and 20,000 µg/L) of polyethylene (PE) microbeads (10-45 µm) for 3 days. The physiological conditions of crabs and a series of biological responses, including DNA damage, antioxidant enzymes activities and their corresponding gene expressions in functional tissues (gills and hepatopancreas) were investigated. PE-MPs accumulated in all tissues of crabs with concentration- and tissue-dependent manner, which was assumed to be via the internal distribution initialized by gills' respiration, filtration and transportation. Significantly increased DNA damages were observed in both gills and hepatopancreas under exposures, however, the physiological conditions of crabs showed no dramatic alterations. Under low and middle concentration exposures, gills energetically activated the first line of antioxidant defense to against oxidative stress, e.g., superoxide dismutase (SOD) and catalase (CAT), but lipid peroxidation damage still occurred under high concentration exposure. In comparison, SOD and CAT composed antioxidant defense in hepatopancreas tended to collapse under severe MPs exposure and the defense mechanism attempted to switch to the secondary antioxidant response by compensatively stimulating the activities of glutathione S-transferase (GST), glutathione peroxidase (GPx) and the content of glutathione (GSH). The diverse antioxidant strategies in gills and hepatopancreas were proposed to be closely related to the accumulation capacity of tissues. The results confirmed the relation between PE-MPs exposure and antioxidant defense in S. serrata, and will help to clarify the biological toxicity and corresponding ecological risks.

Assessment of sulfamethoxazole toxicity to marine mussels (Mytilus galloprovincialis): Combine p38-MAPK signaling pathway modulation with histopathological alterations.

Sulfamethoxazole (SMX), is a ubiquitous antibiotic in the aquatic environment and received concerns on its health hazards, especially its sub-lethal effects on non-target organisms which were remained largely unknown. In the present study, in order to investigate SMX induced tissue damages and reveal underlying mechanisms, marine mussels, Mytilus galloprovincialis were challenged to SMX series (0.5, 50 and 500 µg/L) for six-days followed by six-day-recovery. Comprehensive histopathological alteration (including qualitative, semi-quantitative and quantitative indices), together with transcriptional and (post-) translational responses of key factors (p38, NFκB and p53) in the p38-MAPK signaling pathway were analyzed in gills and digestive glands. Tissue-specific responses were clearly investigated with gills showing more prompt responses and digestive glands showing higher tolerance to SMX. The histopathology showed that SMX triggered inflammatory damages in both tissues and quantitative analysis revealed more significant responses, suggesting its potential as a valuable health indicator. SMX activated expressions of p38, NFκB and p53 at transcriptional and (post-) translational levels, especially after exposed to low level SMX, evidenced by p38 coupled with NFκB/p53 regulation on immunity defense in mussels. Less induction of targeted molecules under severe SMX exposure indicated such signaling transduction may not be efficient enough and can result in inflammatory damages. Taken together, this study expanded the understanding of aquatic SMX induced health risk in marine mussels and the underlying regulation mechanism through p38 signaling transduction.

Progresses on genetic susceptibility of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). Genetic factors might influence susceptibility to the SARS-CoV-2 infection or disease severity. Genome-wide association studies (GWASs) have identified multiple susceptible genes related to COVID-19 phenotypes, providing the scientific basis for the COVID-19 prevention and treatment. In this review, we summarize the recent progresses of COVID-19 susceptible genes, including the GWASs on multiple phenotypes of COVID-19, GWASs of COVID-19 in multiple ethnic populations, GWASs of COVID-19 based on multiple types of genetic variations, and the fine-mapping of the regions surrounding the susceptible genes.

Single-Molecule and Vesicle Trafficking Analysis of Ubiquitination Involved in the Activity of Ammonium Transporter AMT1;3 in Arbidopsis under High Ammonium Stress.

Plants absorb nitrogen from the soil using ammonium transporters (AMTs). Plants can precisely regulate AMT1;3 levels using sophisticated regulatory systems, ensuring adequate nitrogen uptake without hazardous ammonium production. Here, we demonstrated that ubiquitylation can contribute to AMT1;3 degradation under high ammonium stress. Using the ubiquitin site mutant AMT1;3K75R,K233R-EGFP, we demonstrated that the loss of ubiquitination affects the dynamic characteristics of AMT1;3 proteins on the plasma membrane and markedly inhibits the endocytosis of AMT1;3 proteins under high ammonium stress. AMT1;3K75R,K233R-EGFP plants also showed inhibition of protein degradation that targets the vesicular pathway after being exposed to high levels of ammonium. Our findings showed that the dynamic properties, endocytosis, and vesicle trafficking pathways of AMT1;3 proteins are altered in AMT1;3K75R,K233R-EGFP under high ammonium conditions.

Chinese SLE Treatment and Research Group Registry (CSTAR) XIV: the subjective well-being of patients with systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) can significantly influence patients' quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied. Objective: To measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB. Methods: Overall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB. Results: Life satisfaction was significantly lower (p < 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868-0.981, p < 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092-1.230, p < 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022-1.153, p < 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004-1.133, p < 0.05). Conclusion: SWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.

Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies.

As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection. In the present study, we evaluate the activity of nine anti-SARS-CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviruses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which retain their potency against all VOCs tested. At the second part of our study, we reveal the neutralization mechanisms at high molecular resolution of two anti-SARS-CoV-2 neutralizing mAbs by structural characterization. We solve the structures of the Delta-neutralizing ACE2bs mAb TAU-2303 with the SARS-CoV-2 spike trimer and RBD at 4.5 Å and 2.42 Å resolutions, respectively, revealing a similar mode of binding to that between the RBD and ACE2. Furthermore, we provide five additional structures (at resolutions of 4.7 Å, 7.3 Å, 6.4 Å, 3.3 Å, and 6.1 Å) of a second antibody, TAU-2212, complexed with the SARS-CoV-2 spike trimer. TAU-2212 binds an exclusively quaternary epitope, and exhibits a unique, flexible mode of neutralization that involves transitioning between five different conformations, with both arms of the antibody recruited for cross linking intra- and inter-spike RBD subunits. Our study provides additional mechanistic understanding about how antibodies neutralize SARS-CoV-2 and its emerging variants and provides insights on the likelihood of reinfections.