Benefit of cardiac rehabilitation in acute heart failure patients with cognitive impairment.

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

Size Effects of Copper Oxide Nanoparticles on Boosting Soybean Growth via Differentially Modulating Nitrogen Assimilation.

Nanoscale agrochemicals have been widely used in sustainable agriculture and may potentially affect the nitrogen fixation process in legume crops. The present study investigated the size-effects of copper oxide nanoparticles (CuO NPs) on nitrogen assimilation in soybean (G. max (L.) Merrill) plants, which were treated with different sizes (20 and 50 nm) of CuO NPs at low use doses (1 and 10 mg/kg) for 21 days under greenhouse conditions. The results showed that 50 nm CuO NPs significantly increased the fresh biomass more than 20 nm CuO NPs achieved at 10 mg/kg. The activities of N assimilation-associated enzymes and the contents of nitrogenous compounds, including nitrates, proteins, and amino acids, in soybean tissues were greatly increased across all the CuO NP treatments. The use doses of two sizes of CuO NPs had no impact on the Cu contents in shoots and roots but indeed increased the Cu contents in soils in a dose-dependent fashion. Overall, our findings demonstrated that both 20 and 50 nm CuO NPs could positively alter soybean growth and boost N assimilation, furthering our understanding that the application of nanoscale micro-nutrient-related agrochemicals at an optimal size and dose will greatly contribute to increasing the yield and quality of crops.

Bilateral Production Shield Enabling Highly Efficient Perovskite Photovoltaics.

Enhancing the intrinsic stability of perovskite and through encapsulation to isolate water, oxygen, and UV-induced decomposition are currently common and most effective strategies in perovskite solar cells. Here, the atomic layer deposition process is employed to deposit a nanoscale (≈100 nm), uniform, and dense Al2O3 film on the front side of perovskite devices, effectively isolating them from the erosion caused by water and oxygen in the humid air. Simultaneously, nanoscale (≈100 nm) TiO2 films are also deposited on the glass surface to efficiently filter out the ultraviolet (UV) light in the light source, which induces degradation in perovskite. Ultimately, throughthe collaborative effects of both aspects, the stability of the devices is significantly improved under conditions of humid air and illumination. As a result, after storing the devices in ambient air for 1000 h, the efficiency only declines to 95%, and even after 662 h of UV exposure, the efficiency remains at 88%, far surpassing the performance of comparison devices. These results strongly indicate that the adopted Al2O3 and TiO2 thin films play a significant role in enhancing the stability of perovskite solar cells, demonstrating substantial potential for widespread industrial applications.

Robust Gaussian Process Regression Method for Efficient Tunneling Pathway Optimization: Application to Surface Processes.

Simulation of surface processes is a key part of computational chemistry that offers atomic-scale insights into mechanisms of heterogeneous catalysis, diffusion dynamics, and quantum tunneling phenomena. The most common theoretical approaches involve optimization of reaction pathways, including semiclassical tunneling pathways (called instantons). The computational effort can be demanding, especially for instanton optimizations with an ab initio electronic structure. Recently, machine learning has been applied to accelerate reaction-pathway optimization, showing great potential for a wide range of applications. However, previous methods still suffer from numerical and efficiency issues and were not designed for condensed-phase reactions. We propose an improved framework based on Gaussian process regression for general transformed coordinates, which has improved efficiency and numerical stability, and we propose a descriptor that combines internal and Cartesian coordinates suitable for modeling surface processes. We demonstrate with 11 instanton optimizations in three representative systems that the improved approach makes ab initio instanton optimization significantly cheaper, such that it becomes not much more expensive than a classical transition-state theory rate calculation.

Application of surface-modified functional packaging in food storage: A comprehensive review.

Innovations in food packaging systems could meet the evolving needs of the market; emerging concepts of non-migrating technologies reduce the negative migration of preservatives from packaging materials, extend shelf life, and improve food quality and safety. Non-migratory packaging activates the surface of inert materials through pretreatment to generate different active groups. The preservative is covalently grafted with the resin of the pretreated packaging substrate through the graft polymerization of the monomer and the coupling reaction of the polymer chain. The covalent link not only provides the required surface properties of the material for a long time but also retains the inherent properties of the polymer. This technique is applied to the processing for durable, stable, and easily controllable packaging widely. This article reviews the principles of various techniques for packaging materials, surface graft modification, and performance characterization of materials after grafting modification. Potential applications in the food industry and future research trends are also discussed.

Study on dynamic characteristics of cavitation in underwater explosion with large charge.

Underwater explosions (UNDEX) generate shock waves that interact with the air-water interface and structures, leading to the occurrence of rarefaction waves and inducing cavitation phenomena. In deep-water explosions, complex coupling relationships exist between shock wave propagation, bubble motion, and cavitation evolution. The shock wave initiates the formation of cavitation, and their growth and collapse are influenced by the pressure field. The collapsing bubbles generate additional shock waves and fluid motion, affecting subsequent shock wave propagation and bubble behavior. This intricate interaction significantly impacts the hydrodynamic characteristics of deep-water explosions, including pressure distribution, density, and phase changes in the surrounding fluid. In this paper, we utilize a two-fluid phase transition model to capture the evolution of cavitation in deep-water explosions. Our numerical results demonstrate that the introduction of a two-phase vapor-liquid phase change model is necessary to accurately capture scenarios involving prominent evaporation or condensation phenomena. Furthermore, we find that the cavitation produced by the same charge under different explosion depths exhibits significant differences, as does the peak value of cavitation collapse pressure. Similarly, the cavitation produced by different charge quantities under the same explosion depth varies, and the relationship between cavitation volume and charge quantity is not a simple linear increase. The research methods and results presented in this paper provide an important reference for studying the dynamic characteristics of deep-water explosions.

Kinetic Resolution Polymerization Enabled Chemical Synthesis of Perfectly Isotactic Polythioesters.

Isotactic polythioesters (PTEs) that are thioester analogs to natural polyhydroxyalkanoates (PHAs) have attracted growing attention due to their distinct properties. However, the development of chemically synthetic methods for preparing isotactic PTEs has long been an intricate endeavour. Herein, we report the successful synthesis of perfectly isotactic PTEs via stereocontrolled ring-opening polymerization. This binaphthalene-salen aluminium (SalBinam-Al) catalyst promoted a robust polymerization of rac-α-substituted-ß-propiothiolactones (rac-BTL and rac-PTL) with highly kinetic resolution, affording perfectly isotactic P(BTL) and P(PTL) with Mn up to 276 kDa. Impressively, the isotactic P(BTL) formed a supramolecular stereocomplex with improved thermal property (Tm = 204 °C). Ultimately, this kinetic resolution polymerization enabled the facile isolation of enantiopure (S)-BTL, which could efficiently convert to an important pharmaceutical building block (S)-2-benzyl-3-mercapto-propanoic acid. Isotactic P(PTL) served as a tough and ductile material comparable to the commercialized polyolefins. This synthetic system allowed to access of isotactic PTEs, establishing a powerful platform for the discovery of sustainable plastics.

Enhancement of acyl-CoA precursor supply for increased avermectin B1a production by engineering meilingmycin polyketide synthase and key primary metabolic pathway genes.

Avermectins (AVEs), a family of macrocyclic polyketides produced by Streptomyces avermitilis, have eight components, among which B1a is noted for its strong insecticidal activity. Biosynthesis of AVE "a" components requires 2-methylbutyryl-CoA (MBCoA) as starter unit, and malonyl-CoA (MalCoA) and methylmalonyl-CoA (MMCoA) as extender units. We describe here a novel strategy for increasing B1a production by enhancing acyl-CoA precursor supply. First, we engineered meilingmycin (MEI) polyketide synthase (PKS) for increasing MBCoA precursor supply. The loading module (using acetyl-CoA as substrate), extension module 7 (using MMCoA as substrate) and TE domain of MEI PKS were assembled to produce 2-methylbutyrate, providing the starter unit for B1a production. Heterologous expression of the newly designed PKS (termed Mei-PKS) in S. avermitilis wild-type (WT) strain increased MBCoA level, leading to B1a titer 262.2 µg/mL - 4.36-fold higher than WT value (48.9 µg/mL). Next, we separately inhibited three key nodes in essential pathways using CRISPRi to increase MalCoA and MMCoA levels in WT. The resulting strains all showed increased B1a titer. Combined inhibition of these key nodes in Mei-PKS expression strain increased B1a titer to 341.9 µg/mL. Overexpression of fatty acid ß-oxidation pathway genes in the strain further increased B1a titer to 452.8 µg/mL - 8.25-fold higher than WT value. Finally, we applied our precursor supply strategies to high-yield industrial strain A229. The strategies, in combination, led to B1a titer 8836.4 µg/mL - 37.8% higher than parental A229 value. These findings provide an effective combination strategy for increasing AVE B1a production in WT and industrial S. avermitilis strains, and our precursor supply strategies can be readily adapted for overproduction of other polyketides.

Ultrasound radiomics-based artificial intelligence model to assist in the differential diagnosis of ovarian endometrioma and ovarian dermoid cyst.

Background: Accurately differentiating between ovarian endometrioma and ovarian dermoid cyst is of clinical significance. However, the ultrasound appearance of these two diseases is variable, occasionally causing confusion and overlap with each other. This study aimed to develop a diagnostic classification model based on ultrasound radiomics to intelligently distinguish and diagnose the two diseases. Methods: We collected ovarian ultrasound images from participants diagnosed as patients with ovarian endometrioma or ovarian dermoid cyst. Feature extraction and selection were performed using the Mann-Whitney U-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression. We then input the final features into the machine learning classifiers for model construction. A nomogram was established by combining the radiomic signature and clinical signature. Results: A total of 407 participants with 407 lesions were included and categorized into the ovarian endometriomas group (n = 200) and the dermoid cyst group (n = 207). In the test cohort, Logistic Regression (LR) achieved the highest area under curve (AUC) value (0.981, 95% CI: 0.963-1.000), the highest accuracy (94.8%), and the highest sensitivity (95.5%), while LightGBM achieved the highest specificity (97.1%). A nomogram incorporating both clinical features and radiomic features achieved the highest level of performance (AUC: 0.987, 95% CI: 0.967-1.000, accuracy: 95.1%, sensitivity: 88.0%, specificity: 100.0%, PPV: 100.0%, NPV: 88.0%, precision: 93.6%). No statistical difference in diagnostic performance was observed between the radiomic model and the nomogram (P > 0.05). The diagnostic indexes of radiomic model were comparable to that of senior radiologists and superior to that of junior radiologist. The diagnostic performance of junior radiologists significantly improved with the assistance of the model. Conclusion: This ultrasound radiomics-based model demonstrated superior diagnostic performance compared to those of junior radiologists and comparable diagnostic performance to those of senior radiologists, and it has the potential to enhance the diagnostic performance of junior radiologists.

Light-Quality-Adapted Carotenoid Photoprotection in the Photosystem of Roseiflexus castenholzii.

The photosystem of filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii comprises a light-harvesting (LH) complex encircling a reaction center (RC), which intensely absorbs blue-green light by carotenoid (Car) and near-infrared light by bacteriochlorophyll (BChl). To explore the influence of light quality (color) on the photosynthetic activity, we compared the pigment compositions and triplet excitation dynamics of the LH-RCs from Rfl. castenholzii was adapted to blue-green light (bg-LH-RC) and to near-infrared light (nir-LH-RC). Both LH-RCs bind γ-carotene derivatives; however, compared to that of nir-LH-RC (12%), bg-LH-RC contains substantially higher keto-γ-carotene content (43%) and shows considerably faster BChl-to-Car triplet excitation transfer (10.9 ns vs 15.0 ns). For bg-LH-RC, but not nir-LH-RC, selective photoexcitation of Car and the 800 nm-absorbing BChl led to Car-to-Car triplet transfer and BChl-Car singlet fission reactions, respectively. The unique excitation dynamics of bg-LH-RC enhances its photoprotection, which is crucial for the survival of aquatic anoxygenic phototrophs from photooxidative stress.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Imidazolium-Functionalized Conjugated Polymer for On-Site Visual and Ultrasensitive Detection of Toxic Hexavalent Chromium.

Hexavalent chromium [Cr(VI)] is considered a serious environmental pollutant that possesses a hazardous effect on humans even at low concentrations. Thus, the development of a bifunctional material for ultratrace-selective detection and effective elimination of Cr(VI) from the environment remains highly desirable and scarcely reported. In this work, we explore an imidazolium-appended polyfluorene derivative PF-DBT-Im as a highly sensitive/selective optical probe and a smart adsorbent for Cr(VI) ions with an ultralow detection limit of 1.77 nM and removal efficiency up to 93.7%. In an aqueous medium, PF-DBT-Im displays obvious transformation in its emission color from blue to magenta on exclusively introducing Cr(VI), facilitating naked-eye colorimetric detection. Consequently, a portable sensory device integrated with a smartphone is fabricated for realizing real-time and on-site visual detection of Cr(VI). Besides, the imidazolium groups attached onto side chains of PF-DBT-Im are found to be highly beneficial for achieving selective and efficient elimination of Cr(VI) with capacity as high as 128.71 mg g-1. More interestingly, PF-DBT-Im could be easily regenerated following treatment with KBr and can be recycled at least five times in a row. The main factor behind ultrasensitive response and excellent removal efficiency is found to be anion-exchange-induced formation of a unique ground-state complex between PF-DBT-Im and Cr(VI), as evident by FT-IR, XPS, and simulation studies. Thus, taking advantage of the excellent signal amplification property and rich ion-exchange sites, a dual-functional-conjugated polymer PF-DBT-Im is presented for the concurrent recognition and elimination of Cr(VI) ions proficiently and promptly with great prospects in environmental monitoring and water decontamination.

Enzyme-triggered on-demand release of a H2O2-self-supplying CuO2@Fe3O4 nanoagent for enhanced chemodyamic antimicrobial therapy and wound healing.

Nanoagents for chemodynamic therapy (CDT) hold a promising future in the field of antimicrobials, especially copper peroxide (CuO2) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply H2O2. Nevertheless, the poor stability of CuO2 remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@Fe3O4 with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO2-loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO2 nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@Fe3O4 undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO2@Fe3O4. The released CuO2@Fe3O4 then self-supplies H2O2 and generates reactive oxygen species (ROS) within the infected microenvironment through Fenton and Russell effects, to ultimately achieve effective and precise antimicrobial activity. Simultaneously, the magnetic property provided by Fe3O4 allows the substance to be directed towards the infection site. Both in vitro and in vivo tests demonstrated that HA-CP@Fe3O4 exhibited excellent antimicrobial capabilities at low concentration (30 µg mL-1), exceptional biocompatibility and the ability to accelerate wound healing. The findings of this work offer a new and promising approach for targeted and precise CDT.

CD28null T cells in aging and diseases: From biology to assessment and intervention.

CD28null T cells, an atypical subset characterized by the loss of CD28 costimulatory molecule expression, exhibit functional variants and progressively expand with age. Moreover, T cells with these phenotypes are found in both typical and atypical humoral immune responses. Consequently, they accumulate during infectious diseases, autoimmune disorders, cardiovascular conditions, and neurodegenerative ailments. To provide an in-depth review of the current knowledge regarding CD28null T cells, we specifically focus on their phenotypic and functional characteristics as well as their physiological roles in aging and diseases. While uncertainties regarding the clinical utility remains, we will review the following two crucial research perspectives to explore clinical translational applications of the research on this specific T cell subset: 1) addressing the potential utility of CD28null T cells as immunological markers for prognosis and adverse outcomes in both aging and disease, and 2) speculating on the potential of targeting CD28null T cells as an interventional strategy for preventing or delaying immune aging processes and disease progression.

Improved efficiency and stability using a novel elemental sulfur-based moving-bed denitrification process.

Elemental sulfur-based denitrification (ESDeN) technology is known as a cost-saving alternative to its heterotrophic counterpart for nutrient removal from organic-deficient water. However, the traditional fixed-bed reactor (FixBR), as an extensively used process, suffers from a low denitrification rate and even performance deterioration during long-term operation. Herein, we proposed a novel elemental sulfur-based denitrifying moving-bed reactor (ESDeN-MovBR), in which a screw rotator was employed to drive the filled sulfur particles to be microfluidized vertically (a state of vertical-loop movement). Our results showed that the ESDeN-MovBR realized much superior and more stable denitrification performance compared to the ESDeN-FixBR, as indicated by 3.09-fold higher denitrification rate and over one order of magnitude lower intermediates (NO2- and N2O) yield, which could last for over 100 days. Further research revealed that the microfluidization of sulfur particles facilitated the expelling of nitrogen bubbles and excessive biomass, resulting in the prolongation of actual hydraulic retention time by over 80 % and could partially explain the higher denitrification rate in ESDeN-MovBR. The remaining contribution to the improvement of denitrification rate was suggested to be result from changes in biofilm properties, in which the biofilm thickness of ESDeN-MovBR was found to be 3.29 times thinner yet enriched with 2.52 times more autotrophic denitrifiers. This study offered a completely new solution to boost up the denitrification performance of ESDeN technology and provided in-depth evidence for the necessity of biofilm thickness control in such technology.

Insertion of YFP at P5CS1 and AFL1 shows the potential, and potential complications, of gene tagging for functional analyses of stress-related proteins.

Crispr/CAS9-enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context-dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1-pyrroline-5-carboxylate synthetase 1 (P5CS1) is key for stress-induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5' or 3' ends of the endogenous P5CS1 and At14a-Like 1 (AFL1) coding regions. Insertion at the 3' end of either gene generated homozygous lines with expression of the gene-YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT-generated P5CS1-YFP plants revealed new information about P5CS1 localisation and tissue-specific expression. In contrast, insertion of YFP at the 5' end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

Thermodynamic Inhibition of Microbial Sulfur Disproportionation in a Multisubunit Designed Sulfur-Siderite Packed Bioreactor.

Sulfur disproportionation (S0DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S0DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m3/d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m3/d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m3/d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S0DP functional community from S0DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S0DP reaction to +2.56 kJ, thermodynamically suppressing the S0DP occurrence. Therefore, a multisubunit design along with S0DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S0DP in various practical sulfur-packed bioreactors.

ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties.

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.